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Mushrooms  and  Health  
2012  
Report prepared by:
Peter Roupas, Christine Margetts, Pennie Taylor, Debra Krause and Manny Noakes
Pre-Clinical and Clinical Health Substantiation
CSIRO Food and Nutritional Sciences, Australia

Report prepared for:
Mushrooms and Health Global Initiative
July 1, 2012

Commercial in Confidence

Enquiries
All enquiries should be addressed to:
Dr Peter Roupas
Pre-Clinical and Clinical Health Substantiaion
CSIRO Food and Nutritional Sciences
Private Bag 16, 671 Sneydes Road
Werribee, Victoria, 3030
Tel: +61 (3) 9731 3283
E-mail: peter.roupas@csiro.au
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Table of Contents
1. EXECUTIVE SUMMARY ..................................................................................................................................... 7
2. INTRODUCTION ................................................................................................................................................. 12
3. METHODOLOGY ................................................................................................................................................ 13
3.1 EVALUATION OF MEDICAL, SCIENTIFIC AND TECHNOLOGICAL INFORMATION ................................................. 13
3.1.1 Clinical Trials Databases ......................................................................................................................... 14
4. NUTRIENT PROFILING OF MUSHROOMS .................................................................................................. 16
4.1 MACRONUTRIENT AND MICRONUTRIENT CONTENT ........................................................................................... 16
4.2 VITAMINS AND MINERALS ................................................................................................................................. 22
4.2.1 Vitamin D .................................................................................................................................................. 22
4.2.2 Minerals .................................................................................................................................................... 25
4.2.2.1 Selenium .............................................................................................................................................................. 27

5. EFFECTS OF MUSHROOMS AND MUSHROOM COMPONENTS ON HEALTH .................................. 28
5.1 STUDIES IN HUMANS ...................................................................................................................................... 28
5.1.1 ANTI-CANCER STUDIES .................................................................................................................................. 39
5.1.1.1 Breast Cancer ........................................................................................................................................ 40
5.1.1.2 Colorectal Cancer .................................................................................................................................. 42
5.1.1.3 Cervical, Ovarian, Endometrial Cancer ................................................................................................ 44
5.1.1.4 Gastric Cancer ....................................................................................................................................... 44
5.1.1.5 Pancreatic Cancer / Solid Malignancies ............................................................................................... 45
5.1.1.6 Prostate Cancer ..................................................................................................................................... 45
5.1.2 ANTI-MICROBIAL PROPERTIES ....................................................................................................................... 47
5.1.3 ANTI-VIRAL PROPERTIES................................................................................................................................ 48
5.1.4 ASTHMA ......................................................................................................................................................... 48
5.1.5 CARDIOVASCULAR HEALTH ........................................................................................................................... 49
5.1.6 COGNITION / BRAIN HEALTH .......................................................................................................................... 50
5.1.7 CONSTIPATION ................................................................................................................................................ 51
5.1.8 DENTAL HEALTH ............................................................................................................................................ 51
5.1.9 DIABETES ....................................................................................................................................................... 52
5.1.10 DNA DAMAGE ............................................................................................................................................. 52
5.1.11 HEPATITIS ..................................................................................................................................................... 53
5.1.12 IMMUNE FUNCTION ...................................................................................................................................... 53
5.1.13 REPRODUCTIVE HEALTH .............................................................................................................................. 57
5.1.14 SUMMARY OF HUMAN STUDIES .................................................................................................................... 58
6. ANTI-DIABETOGENIC PROPERTIES ............................................................................................................ 59
6.1 Animal model (mouse) studies ..................................................................................................................... 59
6.2 Animal model (rat) studies ........................................................................................................................... 61
6.3 In vitro studies.............................................................................................................................................. 65
6.4 Summary of Anti-Diabetogenic Properties .................................................................................................. 66
7. ANTI-MICROBIAL PROPERTIES ................................................................................................................... 66
7.1 Animal model studies ................................................................................................................................... 66
7.2 In vitro studies.............................................................................................................................................. 67
7.3 Summary of Anti-Microbial Properties ....................................................................................................... 71
8. ANTIOXIDANT PROPERTIES .......................................................................................................................... 71
8.1 PHENOLIC CONTENT .......................................................................................................................................... 75
8.2 ERGOTHIONEINE ................................................................................................................................................ 77
8.3 Summary of Anti-Oxidant Properties........................................................................................................... 78
9. ANTI-VIRAL PROPERTIES .............................................................................................................................. 79
9.1 Summary of Anti-Viral Properties ............................................................................................................... 81
10. EFFECTS ON CARCINOGENESIS ................................................................................................................. 82

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10.1 BLADDER CANCER........................................................................................................................................... 82
10.1.1 In vitro studies (human cell lines) ........................................................................................................... 82
10.2 BREAST CANCER ............................................................................................................................................. 82
10.2.1 Animal model studies .............................................................................................................................. 82
10.2.2 In vitro studies (human cell lines) ........................................................................................................... 83
10.3 CERVICAL, OVARIAN, ENDOMETRIAL CANCER ............................................................................................... 88
10.3.1 Animal model studies .............................................................................................................................. 88
10.3.2 In vitro studies (human cell lines) ........................................................................................................... 89
10.4 COLON / COLORECTAL CANCER ...................................................................................................................... 90
10.4.1 Animal model (mouse) studies ................................................................................................................ 90
10.4.2 Animal model (rat) studies ...................................................................................................................... 91
10.4.3 In vitro studies (human cell lines) ........................................................................................................... 92
10.5 GASTRIC CANCER ............................................................................................................................................ 96
10.5.1 Animal model studies .............................................................................................................................. 96
10.5.2 In vitro studies (human cell lines) ........................................................................................................... 96
10.6 LEUKEMIA ....................................................................................................................................................... 97
10.6.1 Animal model studies .............................................................................................................................. 97
10.6.2 In vitro studies (human cell lines) ........................................................................................................... 98
10.7 LIVER CANCER ................................................................................................................................................ 99
10.7.1 Animal model studies .............................................................................................................................. 99
10.7.2 In vitro studies (human cell lines) ......................................................................................................... 100
10.8 LUNG CANCER ............................................................................................................................................... 101
10.8.1 Animal model studies ............................................................................................................................ 101
10.8.2 In vitro studies (human cell lines) ......................................................................................................... 101
10.9 ORAL CANCER ............................................................................................................................................... 102
10.9.1 In vitro studies (human cell lines) ......................................................................................................... 102
10.10 OVARIAN CANCER ....................................................................................................................................... 103
10.10.1 In vitro studies (human cell lines) ....................................................................................................... 103
10.11 PROSTATE CANCER...................................................................................................................................... 103
10.11.1Animal model (mouse) studies ............................................................................................................. 103
10.11.2 Animal model (rat) studies .................................................................................................................. 104
10.11.3 In vitro studies (human cell lines) ....................................................................................................... 104
10.12 SKIN CANCER .............................................................................................................................................. 107
10.12.1 Animal model (mouse) studies ............................................................................................................ 107
10.12.2 In vitro studies (animal cell lines) ...................................................................................................... 107
10.13 DNA DAMAGE ............................................................................................................................................ 108
10.13.1 Animal model (mouse) studies ............................................................................................................ 108
10.13.2 In vitro studies..................................................................................................................................... 109
10.14 SUMMARY OF ANTI-CANCER PROPERTIES ................................................................................................... 111
11. EFFECTS ON CARDIOVASCULAR HEALTH........................................................................................... 112
11.1 Animal model (mouse) studies ................................................................................................................. 112
11.2 Animal model (rat and larger animal) studies ......................................................................................... 113
11.3 In vitro studies.......................................................................................................................................... 117
11.4 Summary of Cardiovascular Health ........................................................................................................ 118
12. EFFECTS ON NEURODEGENERATIVE DISEASES / COGNITION ..................................................... 118
12.1 Animal model studies ............................................................................................................................... 118
12.2 In vitro studies.......................................................................................................................................... 120
12.3 Summary of Neurodegenerative Diseases / Cognition ............................................................................ 120
13. EFFECTS ON DENTAL HEALTH ................................................................................................................ 120
14. EFFECTS OF EYE HEALTH ......................................................................................................................... 121
15. EFFECTS ON IMMUNE FUNCTION ........................................................................................................... 121
15.1 Animal model (mouse) studies ................................................................................................................. 121
15.2 Animal model (rat) studies ....................................................................................................................... 126
15.3 In vitro studies (human cell lines) ............................................................................................................ 126
15.4 Summary of Immune Function ................................................................................................................. 134
16. EFFECTS ON LIVER HEALTH .................................................................................................................... 134

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17. EFFECTS ON OSTEOPOROSIS / BONE MINERAL DENSITY .............................................................. 135
17.1 Animal model studies ............................................................................................................................... 135
17.2 In vitro studies (human cell lines) ............................................................................................................ 135
17.3 Summary of Osteoporosis/Bone Mineral Density .................................................................................... 136
18. EFFECTS ON RHEUMATOID ARTHRITIS ............................................................................................... 136
18.1 Animal model studies ............................................................................................................................... 136
19. EFFECTS ON WOUND HEALING ............................................................................................................... 137
19.1 Animal model studies ............................................................................................................................... 137
19.2 In vitro studies (human cell lines) ............................................................................................................ 138
20. PROTECTIVE EFFECTS AGAINST UV-LIGHT ....................................................................................... 139
20.1 In vitro studies (human cell lines) ............................................................................................................ 139
21. HYPERSENSITIVITY TO MUSHROOMS IN HUMANS .......................................................................... 140
21.1 Summary of Hypersensitivity Studies ....................................................................................................... 143
22. FOOD SAFETY STUDIES ............................................................................................................................... 143
22.1 Animal Model Studies .............................................................................................................................. 145
22.2 Agaritine .................................................................................................................................................. 147
23. MUSHROOM BIOACTIVE COMPOUNDS AND PROPOSED MECHANISMS .................................... 148
24. MUSHROOM VARIETIES – EFFECTS ON HEALTH .............................................................................. 150
AGARICUS BISPORUS (COMMON WHITE BUTTON, BROWN / CRIMINI, PORTABELLA)............................................... 150
AGARICUS BLAZEI ................................................................................................................................................. 158
AGARICUS BRASILIENSIS ....................................................................................................................................... 170
AGARICUS SYLVATICUS ......................................................................................................................................... 172
AGROCYBE AEGERITE (BLACK POPLAR, PIOPINNO, CHIODINI) ............................................................................. 173
AGROCYBE CHAXINGU .......................................................................................................................................... 174
ANTRODIA CINNAMOMEA ...................................................................................................................................... 174
AURICULARIA AURICULAR (WOOD EAR) .............................................................................................................. 175
AURICULARIA POLYTRICHA (JEW'S EAR) .............................................................................................................. 176
COPRINUS COMATUS.............................................................................................................................................. 177
CORDYCEPS MILITARIS .......................................................................................................................................... 177
CORDYCEPS SINENSIS (CATERPILLAR MUSHROOM) ............................................................................................... 178
FLAMMULINA VELUTIPES (ENOKI) ........................................................................................................................ 180
GANORDERMA LUCIDUM (REISHI, LINGZHI) ......................................................................................................... 184
GRIFOLA FRONDOSA (MAITAKE) .......................................................................................................................... 198
HERICIUM ERINACEUM (POM POM, LION’S MANE) ............................................................................................... 206
HYPSIZIGUS MARMOREUS (BUNA-SHIMEJI)........................................................................................................... 209
INONOTUS OBLIQUUS (CHAGA) ............................................................................................................................. 212
LECCINUM EXTREMIORIENTALE ............................................................................................................................ 212
LENTINULA EDODES (SHIITAKE) ............................................................................................................................ 213
LYOPHYLLUM CONNATUM .................................................................................................................................... 224
PHELLINUS IGNIARIUS ........................................................................................................................................... 224
PHELLINUS LINTEUS .............................................................................................................................................. 225
PHELLINUS RIMOSUS ............................................................................................................................................. 228
PHELLINUS ROBUSTUS ........................................................................................................................................... 229
PHOLIOTA NAMEKO (NAMEKO) ............................................................................................................................. 229
PLEUROTUS CITRINOPILEATUS .............................................................................................................................. 229
PLEUROTUS CORNUCOPIAE .................................................................................................................................... 230
PLEUROTUS ERYNGII ............................................................................................................................................. 230
PLEUROTUS FERULAE ............................................................................................................................................ 233
PLEUROTUS FLORIDA ............................................................................................................................................. 233
PLEUROTUS NEBRODENSIS..................................................................................................................................... 234
PLEUROTUS OSTREATUS (OYSTER MUSHROOMS) ................................................................................................. 234
PLEUROTUS PULMONARIUS ................................................................................................................................... 238
PODAXIS PISTILLARIS ............................................................................................................................................ 239
SCHIZOPHYLLUM COMMUNE (SPLIT GILLS MUSHROOM)...................................................................................... 240

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TREMELLA FUCIFORMIS (WHITE WOOD EAR, WHITE JELLY LEAF) ...................................................................... 241
TRAMETES (=CORIOLUS) VERSICOLOR (TURKEY TAIL, YUNZHI) .......................................................................... 241
VOLVARIELLA VOLVACEA (STRAW MUSHROOM) ................................................................................................. 245
WILD EDIBLE FUNGI.............................................................................................................................................. 246
25. CONCLUSIONS ................................................................................................................................................ 247
26. ABOUT THE AUTHORS ................................................................................................................................. 248
27. APPENDIX – COMPOSITIONAL TABLES: RAW, COOKED AND DRIED MUSHROOMS ............. 251
28. REFERENCES .................................................................................................................................................. 300

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the growing data suggest that the mushrooms and mushroom extracts tested in humans are safe and generally well-tolerated. Furthermore. As they are low in kilojoules. the common white button mushroom (Agaricus bisporus) is a remarkable source of protein. the bioavailability of vitamin D2 from vitamin D2-enhanced button mushrooms via UV-B irradiation was effective in improving vitamin D status and not different to a vitamin D2 supplement. • Mushrooms provide 29% of the recommended daily intake (RDI) for vitamin B2 (riboflavin) and 23% of the RDI for niacin and are one of the very few foods that provide a natural source of vitamin D. which are shown in table 1.g. Pleurotus ostreatus and others) are a valuable source of several micronutrients and are a low kilojoule.g. Mushrooms are low in sodium and high in glutamate which makes them a useful flavour addition to a low-salt diet. Executive Summary • Nutritional Profiling: The current review of nutritional data identified an additional 31 mushroom varieties (since the 2010 report). The human trials carried out to date have primarily been smaller observational studies. This report now provides nutritional profiles for a total of 103 mushroom varieties. although larger.1. Agaricus bisporus/white. • Cultivated mushrooms (e. double-blind. In general. placebo controlled human studies have recently been completed and several others are in progress. nutrient-dense food. Agaricus bisporus/brown. during drying). In vitro and animal trials have reported an inhibition of aromatase activity and subsequent reduction of estrogen 7 . Lentinus edodes.Vitamin D is an important factor for immune function. they are ideal for incorporation in weight loss programs. magnesium and vitamin D. phosphorus. The most promising data appear to be those indicating an inverse relationship between mushroom consumption and breast cancer risk. A recent human clinical trial has demonstrated the bioavailability of vitamin D2 from UV-Birradiated button mushrooms in healthy adults deficient in serum 25-hydroxyvitamin D. Biosynthesis of vitamin D levels from ergosterols in mushrooms can be significantly enhanced by exposure to sunlight or ultraviolet light post-harvest (e. • Human Studies: The properties and mechanisms of extracts and bioactive compounds from mushrooms that have been evaluated in a human population or human cell lines are discussed in this report. • In comparison to common vegetables.

which provides a physiologically-relevant mechanism for effects on estrogen receptor positive tumors. • Anti-Cancer Properties: Anti-tumor effects. NF-kappaB.. and therefore such effects have not yet been scientifically validated in humans. 2011). which mirror decreases in plasma glucose. Pleurotus ostreatus (oyster). involve the elevation of natural killer (NK) cell numbers and the stimulation of inducible nitric oxide (NO) synthase gene expression. A decrease in aromatase activity has recently been demonstrated in a human trial following consumption of Agaricus bisporus (Palomares et al. A small number of studies in animals have been undertaken and suggest that the anti-microbial effects in vivo may be mediated via the immune system. • Anti-Oxidant Activity: A recent (2012) comparison of the antioxidant properties and phenolic profile of the most commonly consumed fresh cultivated mushrooms and their mycelia produced in vitro: Agaricus bisporus (white and brown). Pleurotus eryngii (king oyster) and Lentinula edodes (shiitake) have reported that 8 . Anti-tumor effects of proteoglycan fractions from a variety of mushrooms. While studies in human cell lines provide supporting evidence. have been reported for polysaccharides extracted from various mushrooms. cholesterol and triglyceride concentrations. a number of human trials have been undertaken and these are outlined in this report. strengthens the level of evidence for anti-diabetogenic effects of the studied mushrooms and their extracts. • Anti-Microbial Properties: Initial studies in humans have suggested anti-microbial properties of extracts from Agaricus blazei Murill and Ganoderma lucidum. Activation of NK cells is likely via interferon-gamma and interleukin mediated pathways. The polysaccharides generally belong to the beta-glucan family of compounds and appear to exert their antitumorigenic effects via enhancement of cellular immunity. well-designed human clinical trials are required before anti-cancer health outcomes in humans can be validated. Anti-microbial effects of a large number of mushroom varieties and mushroom components on both gram-positive and gram-negative bacteria have been confirmed via in vitro studies. primarily in human cell lines. although these studies did not have adequate controls in the experimental design. blood pressure.by mushroom extracts. • Anti-Diabetogenic Effects: The consistency between the effects of mushroom extracts in diabetic animal models and preliminary data from human trials. In recent years. which is then followed by NO production in macrophages via activation of the transcription factor. including Agaricus bisporus.

Plasma cholesterol in animal models has been shown to be reduced by mushroom consumption.e. while L. and other biomarkers of cardiovascular risk have been demonstrated by consumption of mushroom fibre. which were not present when infusion was undertaken over a shorter period. Inhibitory effects on hepatitis B and herpes simplex virus type I have also been reported. similar effects on cholesterol. Ergothioneine has been shown to have anti-oxidative/anti-inflammatory properties in several edible mushrooms. • Immune Function: A recent systematic review of immunomodulatory dietary polysaccharides concluded that glucan extracts from Trametes Versicolor improved survival and immune function in human randomised controlled trials of cancer patients. the two enzymes of paramount importance to the life cycle of the HIV. via balance of T cells and their cytokine production. The antioxidant activities appear to be related to the polyphenolic content. providing a high level of evidence for these effects. however. The hypocholesterolemic effect in animal trials appears to be due partly to an increased rate of low density lipoprotein and high-density lipoprotein catabolism. Some side effects were observed at the highest dosages used. Proteins. L-ergothioneine is a biologically active antioxidant and its production in mushrooms can be enhanced by addition of histidine to the growth medium/compost. however a number of studies have reported inhibitory effects at the initial stage of virus replication. effects on low density lipoprotein and high-density lipoprotein have generally not been observed. they do not kill the virus). • Cardiovascular Health: A reduction in total cholesterol following mushroom consumption has been reported in a number of human trials. • Anti-Viral Properties: Two Phase I/II trials in HIV-positive patients have been undertaken with lentinan.Agaricus bisporus (brown) had the highest antioxidant potential in vitro. peptides and polysaccharopeptides from mushrooms have been reported to be capable of inhibiting human immunodeficiency virus type 1 (HIV-1) reverse transcriptase and protease. Significant antioxidant activities in vitro have been reported in several varieties of mushrooms. The anti-viral effects of mushrooms do not seem to be related to viral adsorption or virucidal effects (i. with one study reporting antioxidant capacity comparable to vitamin C. macrophages. a beta-glucan from Lentinus edodes. edodes possessed the highest reducing power. While some studies have postulated eritadenine or angiotensin I – converting enzyme inhibitory peptides as the hypocholesterolemic agents. and via the 9 . Many of the potential therapeutic effects of mushrooms and mushroom components on a variety of diseases appear to be directly or indirectly mediated by enhancing natural immunity of the host via effects on natural killer (NK) cells.

the data have shown no evidence of clinical problems 10 . as have several human clinical trials. data showing protective effects of mushrooms (Hericium erinaceum) on beta-amyloid peptide toxicity in the brain and mild cognitive impairment (both precursors to dementia) appear promising. primarily in Japan. while mice fed calcium plus vitamin D2-enhanced (UV irradiated) mushrooms showed improved bone mineralization through a direct effect on the bone. and hence this condition has been referred to as ‘mushroom worker’s disease’. the growing conditions are important in maintaining a healthy nutritional profile for mushrooms. where air-quality may be poor. so these effects remain to be confirmed in larger well-designed human trials. Preliminary human trials with Hericium erinaceum derivatives showed efficacy in patients with dementia in improving the Functional Independence Measure score or retarding disease progression. and by inducing the expression of calcium-absorbing genes in the duodenum and kidney. The small number of cases reported. or after corticosteroid administration via a nasal spray. either without medication. The human trials carried out to date have suggested that the mushrooms and mushroom extracts tested are safe and generally well-tolerated. • Hypersensitivity to Mushrooms: Spores of mushrooms are airborne components and can be the cause of hypersensitivity / respiratory allergy. when the affected person is removed from the factory environment. In general. • Osteoporosis / Bone Health: In vitro studies have reported positive effects of mushroom extracts on mineralisation of osteoblastic cell lines. The human trials to date have generally had low statistical power. • Bio-accumulation: Mushrooms can bioaccumulate undesirable levels of compounds such as mercury and cadmium when grown in polluted ecosystems or on agro-industrial waste and therefore. • Cognition / Brain Health: Although preliminary.activation of Mitogen Activated Protein Kinase (MAPK) pathways. The symptoms for this condition usually improve rapidly. have usually involved workers in the commercial production of mushrooms. A trial with 50 to 80-year-old Japanese men and women diagnosed with mild cognitive impairment reported significantly increased cognitive function scores compared to placebo during intake. Animal studies have reported increased bone density following consumption of mushroom extracts. • Food Safety Studies / Agaritine: A number of safety assessments on consumption of mushrooms and mushroom extracts have recently been undertaken by the European Food Safety Authority (EFSA).

with respect to blood test results. hepatic and renal function. Similarly. 11 . glucose and lipid metabolism. blood pressure or DNA toxicity. analysis of agaritine from hot-water extracts of the mushroom Hatakeshimeji showed no clinical effects in a human trial suggesting that the extract of Hatakeshimeji was safe for consumption.

. 2011). Such mushroom polysaccharides are beginning to be evaluated as adjuvant cancer therapy compounds alongside conventional cancer treatments (Standish et al. bioactive proteins from mushrooms (such as lectins. although structure–function relationships have been described between antitumor activities and structural characteristics of β-D-glucans. Chen et al. 2008).. The mechanisms by which these polysaccharides exert their immunomodulatory effects are not entirely clear. 2006) and subsequent reduction of estrogen. but have been shown to enhance hostmediated immunomodulatory responses (reviewed by Wong et al.3-β-glucans which have been reported to inhibit tumor growth by stimulating the immune system via activation of macrophages. fungal immunomodulatory proteins (FIP). via balance of T helper cell populations and subsequent effects on natural killer (NK). A recent systematic review has also provided evidence for immunomodulatory effects (increased NK cell activity. but growing. 2011).2. number of direct human intervention trials. anti-tumor. 2008). cells and also via cytokine production (Hetland et al. anti-viral and immunomodulatory activities (Xu et al. Other work has implicated polysaccharides with varying sugars such as beta.. Although there are still a limited. 12 . anti-microbial effects and hypocholesterolemic effects. 2010). ribonucleases and other proteins have also been reported to possess similar anti-tumor. 2011b). IgM.6-branched 1. ribosome inactivating proteins (RIP). there is a very large number of in vitro and in vivo animal trials describing a range of possible health benefits including immunomodulatory. Some of the more efficacious compounds in mushrooms are 1. neutrophil and leukocyte counts) in humans from oral ingestion of dietary polysaccharides (glucans) from some varieties of mushrooms (Ramberg et al. is a potential adjuvant therapy for breast cancer patients with estrogen receptor positive tumors. 2001. while inhibition of aromatase activity by mushroom extracts (Grube et al. These mushroom polysaccharides generally do not exert cytotoxic effects on tumor cells. effects on IgG. Introduction Alongside the mushrooms’ long history as a food source is an equally long history of beliefs about their curative abilities in traditional medicine systems—both the folk medicine of the western world and traditional medicine of the orient. While the effects and underlying mechanisms of mushroom polysaccharides in health outcomes have been more extensively evaluated..and alpha-glucans (Borchers et al.

000 journals across 4.000 major journals across 164 scientific disciplines. Asian. scientific and technical literature based on the mushroom varieties and health conditions identified in the research proposal. and technical reports covering all aspects of primary international information sources in agriculture and related fields.an abstract database covering 25 million abstracts from over 16. theses. monographs. The literature cited is mainly in English. The captured records were cross-checked across the above databases as well as with records 13 . The latter part of this report identifies and describes the individual key studies undertaken for several culinary and medicinal mushrooms. 3. and to identify areas where future human dietary intervention trials are warranted to substantiate the potential effects of mushroom consumption on human health outcomes. AGRICOLA .This report evaluates published human trials on mushroom consumption and health outcomes in order to identify the levels of evidence. particularly where they provide insights into cellular mechanisms.1 Evaluation of Medical. audiovisual materials. Scientific and Technological Information The information on mushrooms and health was sourced via detailed and thorough strategic electronic searches of medical. SCOPUS . patents. Slavic. Methodology 3. animal and in vitro studies that provide lower levels of evidence are also discussed.000 publishers.includes bibliographic citations for journal articles. The systematic literature searches were carried out using the following databases: PubMed – a service of the US National Library of Medicine that includes over 16 million citations from the MEDLINE database and other life science journals. proceedings.000 e-journals). and African languages. computer software. While the report focusses on human studies. CSIRO Electronic Journals Collection (4. Web of Science – 10. but over one-third of the database comprises citations in Western European. translations.

Searches for clinical trials were updated on June 15.from Food Science and Technology Abstracts (FSTA).1 Clinical Trials Databases The search strategy aimed to find published English language studies. An initial limited search of MEDLINE was undertaken followed by analysis of the text words contained in the title and abstract. • Current ongoing trials and as-yet-unpublished trials that might yield data were identified using the following databases: • Clinical trials. The following databases were searched for systematic reviews and clinical trials: • Medline on Pub Med • Science Citation Index (searched on CSIRO Network) • Cochrane Central (Database of Systematic Reviews and Cochrane Collaboration Central Register of Controlled Trials. 2012. The journals with high impact factors and scientific credibility are indexed in these databases. The listing of the sources and databases used is provided below. The searches were completed in May 2012 and the database contains papers published up to this time. • Joanna Briggs Institute (JBI) Library of Systematic Reviews. was then undertaken across all included databases.gov 14 .1. MESH and index terms. using identified keywords. Epidemiological and clinical trials were also included in the review and evaluations. A second search. A three-step search strategy wws utilised to complete the report. NHS Economic Evaluation Database (NHS EED). Thirdly. 3. Health Technology Assessment (HTA) Database) CRD Centre for Reviews and Dissemination. • Centre for Reviews and Dissemination Databases (Database of Reviews of Effects (DARE). the reference list of identified reports/trials and articles was searched for additional studies. and of the index terms used to describe relevant articles. Cambridge Scientific Abstracts (CSA) and ISI Proceedings.

India • German Clinical Trials Register • Iranian Registry of Clinical Trials • Japan Primary Registries Network • Sri Lanka Clinical Trials Register • The Netherlands National Trial Register The searches did not include unpublished and non peer-reviewed studies. 15 .gov Register • Cochrane Collaboration Central Register of Controlled Trials • Australian and New Zealand Clinical Trials Registry (ANZCTR) • World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) portal which includes the following sub-files: • Australian New Zealand Clinical Trials Registry • ClinicalTrials.• ISRCTN International metaRegister of Current Controlled Trials which includes the following sub-files: • Action Medical Research (UK) • Medical Research Council (UK) • UK Trials (UK) • The Wellcome Trust (UK) • NIHR Health Technology Assessment Program (HTA) (UK) • NIH Clinical Trials.gov • ISRCTN • Chinese Clinical Trial Registry • Clinical Trials Registry .

canned in brine solids (Jap) Mushroom. EAR (Estimated Average Requirement) and AI’s for females and males of different ages for comparison. boiled (Jap) Kuroawabitake. straw. raw (USDA) Culinary Specialty Mushrooms Morel. raw (USDA) Shiitake. boiled (Jap) Shimeji Hatakeshimeji. canned in brine. canned in brine. drained (Aust) Mushroom Boletus. Asian. boiled. boiled (Jap) Matsutake.4. vitamin and mineral contents of raw/fresh.1 Macronutrient and micronutrient content The current review of nutritional data identified an additional 31 mushrooms varieties (since the 2010 report). The compositional data has been tabulated agains RDI’s. This report now provides nutritional profiles for a total of 103 mushroom varieties. raw (Can) Mushrooms. white microwaved (Can) Mushroom Brown Italian (Crimini) raw (Can) Boletus edible (Fin) Matsutake. dried (Log grown) Mushroom Milk Caps. shown in table 1. raw (Jap) DRIED MUSHROOMS Chanterelle. drained (Aust) Mushroom. raw (Jap) Tree ears. Russula (Fin) Mushroom fried Agaricus bisporus (Fin) Chantarelle (Fin) Boletus edible. Kiurage. raw (Jap) Tree ears. boiled (Fin) False Morel (Fin) Mushroom. grilled (Can) Shimeji Honshimeji. drained solids (USDA) Culinary Specialty Mushrooms Numeisugitake. raw (Jap) Mushroom. Nutrient Profiling of Mushrooms 4. canned. drained with salt (Can) Milk-cap Northern (Fin) Mushroom. Summary tables are also provided. raw (Jap) Mushroom Portabella (Portabello). straw. canned. raw (Jap) Tree ears. dried and culinary specialty varieties of the common mushroom varieties found in Appendix 1 of this report. raw (Jap) Culinary Specialty Mushrooms Tamogitake. Arage-kikurage. 16 . Shiro-kikurage. Asian. salted (Fin) Of particular interest for this report are the nutrients for which the common mushroom varieties provide >10% recommended dietary intake (RDI) or Adequate Intake (AI) for Adults 19 years and over by 100g (20g for dried mushroom varieties) with comprehensive compositional tables for the macronutrient contents. Table 1: Mushroom varieties added to 2012 Report RAW MUSHROOMS COOKED MUSHROOMS Common Mushroom (Agaricus Bisphorus) Common Mushroom (Agaricus Bisphorus) Mushroom Portabella (Portobello). straw. canned. drained solids (Can) Yanagimatsutake. golden.

Although the concentration of protein in mushrooms is low. Ten popular species of both edible and medicinal Korean mushrooms have been analysed for their free amino acids and disaccharides. which applies to animal protein sources. the use of mycoprotein has been exploited in the manufacture of meat replacement products such as Quorn. where the edible mushrooms 17 .3 Fat (g) 1. As shown in Tables 2 and 3. Protein quality of mushrooms has not been extensively investigated.3 Protein (g) 0. 2 Content Nutrient 3.fresh weight 100g. edible mushrooms and medicinal mushrooms was 91. The average total of free amino acids for all mushrooms. Agaricus blazei (227. The average total carbohydrate concentration was 46.13 mg/g.a method of evaluating the protein quality based on the amino acid requirements of humans – is approximately 0. The average total free amino acid concentration was 121 mg/g in edible mushrooms and 61 mg/g in medicinal mushrooms.66 assuming a digestibility of 70%. Inonotus obliquus (2.00 mg/g) showed the lowest concentration among the 10 species of mushrooms.3 Carbohydrate (g) 0. The highest score is 1. Common mushroom (Agaricus bisporus) macronutrient content .00 mg/g) showed the highest concentration of total free amino acids. The amino acid profile of common mushroom protein suggests the Protein Digestibility Corrected Amino Acid Score (PDCAAS) . Australian nutrient composition data. this suggests a moderate protein quality.67 mg/g in the 10 species of mushrooms.5 Fibre (g) 25 / 103 Energy (kcal/kj) As a food. As such. the common white button mushroom is low in energy and a valuable source of fibre and several micronutrients.Table 2. Studies of protein quality in other species suggest a lower score. on the other hand. respectively. mushrooms are low in protein providing 2-3g/100g raw weight.

. The nutrients for which mushrooms provide >10% of the recommended daily intake (RDI) for Australian adults are riboflavin. Mushrooms remain one of the very few foods that provide a natural source of vitamin D. vitamin D. or flesh. The carbohydrate constituents of the 10 mushroom species were mainly mannose (36. glucose (34. The concentration of vitamin B12 in mushrooms has been controversial. Mushrooms cultivated on manure-enriched compost may contain vitamin B12 and may be responsible for previous reports of high B12 levels. HPLC and mass spectrometry showed the vitamin B12 retention time and mass spectra to be identical to those of the standard vitamin B12 and those of food products including beef. egg. niacin. In addition. It is of note that mushrooms provide 26% for males and 31% for females of the recommended daily intake (RDI) for Vitamin B2 (riboflavin) and 23-27% of the RDI for niacin per 100g respectively for adults over 19 years. and milk but not of the pseudovitamin B12. and xylose (16. phosphorus and selenium. Nevertheless.07µg. the USDA database suggests that vitamin B12 at 0.contained 66.68 mg/g and the medicinal mushrooms contained 26.. the presence of any vitamin B12 is intriguing. Further investigation of this is warranted. salmon. Mattila and co-workers (Mattila et al. mushrooms provide 22-26% of the RDI for selenium and 20-29% of the adequate intake (AI) for copper for males and female over 19 years respectively. suggesting that the vitamin B12 is probably bacteria-derived (Koyyalamudi et al. 2009a). stalk.2µg of Vitamin D. The vitamin D levels can be significantly enhanced by sunlight or irradiation. However. 2009b). which also shows the estimated average requirement (EAR) and recommended daily intake (RDI) for Australian adults that is provided by a 100g serve of mushrooms.83%) (Kim et al. 2001) reported levels of 0..65 mg/g. The micronutrient content of the common mushroom (Agaricus bisporus) is shown in Table 3.2µg (USDA). Agaricus bisporus (USDA) is of particular interest in this area showing that 100g of mushroom exposed to UV light can provide up to 11. A recent study of vitamin B 12 concentrations in Agaricus bisporus reported higher concentrations of vitamin B12 in the outer peel than in the cap. as conventionally only animal sources are thought to provide vitamin B12. an inactive corrinoid in humans.05-0.23%).04µg per 100g mushrooms is very low compared to the RDI of 2µg/day. Mushrooms are also low in sodium and low in kilojoules. a significant increase in vitamin D when compared to non-exposed Agaricus bisporus providing 0. High concentrations of vitamin B12 were also detected in the flush mushrooms including cups and flats. beef liver.70%). 18 .

058 1 AI 1.94µg & 1. AI rises after 50 years.Table 3.9 30 AI 36 AI 1.15 19 AI 29 AI 8.6 5 Riboflavin (B2) (mg) 4 Niacin equivalents (B3) (mg) Folate (mcg.2 4 AI 4 AI 0. 1 μg in the Finnish & Danish data 11 19 .0 3 2 3 2 13 = 2 µg RE <1 <1 <1 <1 0. Micronutrient content: Fresh weight/100g of common mushroom (Agaricus bisporus) Australian 1 2 nutrient composition data (unless otherwise specified) RDI and EAR for Australian adults >19years of age. =µg) Vitamin B6 (mg) 5 Pantothenic acid (mg) Biotin (µg) 6 7 Vitamin C (mg) Beta-carotene equivalent 8 (µg) Vitamin D (µg) Copper (mg) 9 10 Phosphorus (mg) Magnesium (mg) Manganese (mg) Molybdenum (µg) Sodium (mg) 4 5 4 8.27 5 3 3 2 3 <1 <1 <1 <1 Potassium (mg) Selenium µg) Zinc (mg) Iron (mg) 1 AI Calcium (mg) Iodine (µg) 18 17 14 0 Nil 11 AI Nil Nil Nil 1 RDI – Recommended Daily Intake EAR – Estimated Average Requirement 3 Percentages have been rounded to whole numbers 4 The RDI and EAR for riboflavin for adults >70 years is higher than adults <70 years 5 The RDI and EAR for Vitamin B6 acid rises after 50 years 6 Adequate Intake (AI) used as no RDI or EAR determined 7 AI used as no RDI or EAR determined 8 6 µg all-trans β-carotene = 1 µg Retinol Equivalent 2 9 Australian Vit D composition data are not available.342 20 AI 29 AI 110 19 11 19 11 11 10 3 3 4 3 12 0.56 5 4 9 7 16 0.90 µg respectively. US data was used 16 Iron requirements for women reduce after the age of 50 17 Calcium requirements increase after the age of 50 in women and 70 in men 18 Iodine μg is 0 in the Australian & USDA data.0 13 310 8 AI 15.37 34 29 41 34 3.02 2 2 2 2 1. Data from Germany & Canada report higher levels of Vit D of 1. USDA data was used. 3 Nutrient Content % EAR % RDI % EAR % RDI Female Male Male Female 0.025 3 2 3 2 Thiamin (B1) (mg) 0. 3μg in the UK data. 10 AI used as no RDI or EAR determined The RDI and EAR is higher for adults>31 years therefore % RDI/EAR reduce accordingly 12 AI used as no RDI or EAR determined 13 It was not thought meaningful to include a % RDI or EAR for sodium 14 AI used as no RDI or EAR determined 15 Australian zinc composition data not available.4 26 22 31 26 15 0.72 31 23 34 27 18 6 5 6 5 0. AI was used as no RDI or EAR determined.

It lessens the effect of salt on blood pressure. as mushrooms obtain a range of essential nutrients from soil growing medium such as phosphorus. copper and selenium. Table 4 identifies the absolute mineral content for these minerals for ease of comparison. The compositional tables (Appendix 1) identify the American nutrient composition data for 100g of raw weight of common white mushroom (Agaricus Bisporus). there are greater variances within the composition for these nutrients. deficiency of pantothenic acid is very rare. Potassium is an important electrolyte in the body and is the major cation within cells. Mushrooms are also a good source of potassium. niacin and pantothenic acid are similar. some hormones and neurotransmitters. CoA plays an important role in the synthesis of fatty acids. deficiency is very unusual and has been seen rarely in people on total intravenous nutrition. amino acids (the building blocks of protein). people with kidney disease should be aware that mushrooms are high in potassium. 20 . The nutrients providing > 10% of the Recommended Dietary Allowance (RDA) and Allowable Intake (AI) for American males and females respectively over 19 years using USDA Dietary Reference Intakes are: • Riboflavin (B2) provide 28 -35% RDA • Niacin (B3) providing 23 -26% RDA • Pantothenic acid providing 25-37% AI • Phosphorus providing 9%-9% RDA • Copper providing 19-27% RDA • Selenium providing 13-16% RDA In comparison with Australian grown mushrooms. the composition for riboflavin. However. Biotin is necessary for a number of enzyme reactions in the body. Pantothenic acid is involved in fatty acid metabolism and is necessary for the production of coenzyme A (CoA). as they may need to limit their potassium intake.Mushrooms contain valuable amounts of the nutrients biotin and pantothenic acid. Like biotin. However.

12 Pumpkin. sweet. raw 0.83 6.7 Sweet potato. yellow. with leaf and stalk vegetables consumed less frequently.93 9. corn and beans.1 2 3 0. the common mushroom (Agaricus bisporus) is a remarkable source of protein. Other notable vegetables in order of those most commonly consumed were tomatoes and tomatoe products.4 9. magnesium and vitamin D. raw 1.24 0.5 2. In comparison to common vegetables. raw 1. Common. raw 2. green.58 Broccoli.000mg/d: USDA RDA Male and female >19years = 700mg/d Aust RDI Male > 19 years = 1.6 2.7mg/d. Raw 20 21 . carrots and root vegetables.97 Potatoes.0 6.4 86/360 86/359 26/109 41/173 34/141 31/131 69/288 Aust RDI Male and female >19years = 1.05 0.37 0. raw 3. flesh and skin.5 Carrots.3 Bisporus) Corn. Female > 19 years = 1. peas.318 20 21 Selenium (µg) 15.64 Beans. White. snap. cabbage. cauliflower and brassica vegetables. raw 1.3 18.3 0. Agaricus bisporus data source Australian composition data 23 USDA Composition data 19 Phosphorus (mg) 110 86 22 Minerals Copper (mg) 0.35 0. Release 24 (2011) 19 Fat (g) Fibre (g) Energy (Kcal/KJ) 0. unprepared 1.Table 4: Key mineral content for 100g raw weight of Agaricus bisporus USDA and Australian data.71 USDA National Nutrient Database for Standard Reference.68 15. phosphorus. white.9mg/d 21 Aust RDI Male > 19 years = 70 μg/d Female > 19 years =60 μg /d: USDA RDA Male and female >19years = 55μg/d 22 Obtained Online NUTTAB 2006 Nutrient Database – Mushroom.5 25/103 1.2mg/d: USDA AI male and female >19 years = 0.342 0. raw.82 6. other common vegetables .macronutrient content per 100g Protein (g) Carbohydrate (g) Common Mushroom (Agaricus 3.3 1. Table 5 Common mushroom (Agaricus Bisporus) vs.7 2.8 2.22 0.57 20. The macronutrient of the common mushroom (Agaricus bisporus) compared to the other commonly consumed Australian vegetables is displayed in Table 5 and Table 6. Raw 23 Obtained USDA Nutrient database .Mushroom.3 Key Nutrient Comparisons of the common mushroom white (Agaricus bisporus) vs commonly consumed vegetables (Australian Data) The 1995 National Nutrition Survey (NNS) identified that potatoes were the main contributor to the mean intake of vegetable products and dishes.1 0.

0 0.8 0.27 0.05 0.03 0. snap.2 0.141 12.093 6. 2009b). 2011). randomized.061 0.61 0.7 62 21 0.052 0.02 1 110 10 0. Agaricus bisporus mushrooms contain an abundance of ergosterol.175 9 5..209 2. placebo-controlled trial (registered at http://germanctr.2.203 19.0 0.0 0.8 89 37 0. raw Carrots.2 Vitamins and Minerals 4. raw Sweet potato.2 0.066 0.071 18 0.0 0.138 0. unprepared Pumpkin.0 0. yellow.155 42 0.Table 6 Common mushroom (Agaricus bisporus) micronutrient (vitamin) content per 100g Australian Nutrient Composition Data Vs Commonly consumed vegetable (Aust and USDA). green..073 1. Vitamin D2 was well absorbed and metabolized as shown by the serum response of 25-hydroxyvitamin D in rats fed the irradiated mushrooms. The stability of vitamin D2 remained unchanged during storage at 4ºC and at room temperature over 8 days indicating no degradation of vitamin D2.082 33 0.025 Folate (mcg) Vitamin B6 (mg) Vitamin C (mg) Phosphorus (mg) Magnesium (mg) Iron (mg) Vitamin D (µg) 18 0. Common Mushroom (Agaricus Bisporus) Corn. Furthermore. 4. raw Potatoes.1 Vitamin D A single-blinded. raw Beans. which on exposure to UV irradiation is converted to vitamin D2. 22 .4 47 25 0.de as DRKS00000195) in 26 young subjects with serum 25-hydroxyvitamin D (25OHD) < 50 nmol/l undertaken over a 5 week period has demonstrated the bioavailability of vitamin D2 from UV-Birradiated button mushrooms in healthy adults deficient in serum 25-hydroxyvitamin D.9 89. the bioavailability of vitamin D2 from vitamin D2enhanced button mushrooms via UV-B irradiation was effective in improving vitamin D status and not different to a vitamin D2 supplement (Urbain et al. 2010).0 The nutritional and health benefits of mushrooms have recently been reviewed (Cheung. raw. sweet.078 11 0. white.3 . flesh and skin. A high rate of conversion from ergosterol to vitamin D2 has been reported following a short treatment time (Koyyalamudi et al.52 NA 0. raw Thiamin (B1) (mg) 0. raw Broccoli.2 44 35 66 38 12 12 21 25 0.071 16 19 63 0.

In weanling female rats. Growth is unaffected by UV-B. and Grifola frondosa (Dicks. amino acids. 2012).0% light-exposed mushrooms significantly raised 25-hydroxyvitamin D (25(OH)D) and suppressed parathyroid hormone levels compared to control-fed rats or rats fed 5. Vitamin D2 from UVB-exposed mushrooms was reported to be bioavailable.000. niacin.. because 25hydroxycholecalciferol (25(OH)D3) decreased proportionally in serum (Stephensen et al.5% and 5. folate. 2. The effects of UVB on Agaricus bisporus are limited to changes in vitamin D and show no detrimental changes relative to natural sunlight exposure. Enrichment of vitamin D2 in Agaricus bisporus white button mushroom using continuous UV light needs a longer exposure time. Vitamin D2 can be increased by UV-B exposure during the growth phase of Agaricus bisporus. to 46. Postharvest exposure to supplementary UV-B resulted in a higher vitamin D2 content of 32 µg/100 g compared to 24 µg/100 g obtained from exposure to UV-B during the growth phase (Kristensen et al. On a dry weight basis. which can lead to discoloration. 2012).F. Six to eight hours of sunlight exposure stimulated the production of vitamin D from low levels of 134.. A recent randomised controlled trial of 38 adults consuming ergocalciferol from Agaricus bisporus or supplements for 6 weeks has reported that ergocalciferol was absorbed and metabolized to 25hydroxyergocalciferol (25(OH)D2) but did not affect vitamin D status. 2011). and 469 IU. Ganoderma lucidum (W. Gray (Maitake). Curt.5%) (Simon et al. however.:Fr. ergosterol. 2005). safe.900 IU vitamin D.:Fr. and functional in supporting bone growth and mineralization in a growing rat model without evidence of toxicity (Calvo et al.) Lloyd (reishi). vitamins B 6. and 31.) S. or agaritine were observed following UVB processing.These data are in agreement with an earlier report that showed that Vitamin D2 from UVirradiated mushrooms was well absorbed and metabolized in a rat model system and significant increases in femur bone mineralization was shown in the presence of vitamin D-2 from irradiated mushrooms compared with the controls (Jasinghe et al. evidence of folate oxidation. The 23 .. respectively. Exposing white button mushrooms to ultraviolet B (UVB) light markedly increases their vitamin D2 content.. 66. 2012). diets containing 2. The effect of sunlight on the production of vitamin D of indoor-grown mushrooms while drying has been studied using Lentinus eddoes (Berk.0% mushroom unexposed to light. 2011). riboflavin. while exposure to sunlight resulted in a 26% loss of riboflavin..) Singer (Shiitake mushroom). respectively. vitamin B 5. fatty acids.760. exposure of whole or sliced mushrooms to pulsed UV light significantly increased vitamin D2 without any observed discoloration (Rao Koyyalamudi et al.. and unexplained increases in ergosterol (9. no significant changes in vitamin C.

. the concentration of vitamin D2 produced in Agaricus bisporus was 3. In contrast. the concentration of vitamin D 2 produced was 3. An intensity of 1.5 J/cm2. respectively (Teichmann et al. so the sunlight-activated biosynthesis of vitamin D from ergosterols within mushrooms has substantial implications for the mushroom industry in the context of health (Stamets. Oyster mushrooms (Pleurotus ostreatus).m.7–2. UV-B. Post-harvest time did not have a 24 . whereas using an intensity of 0.83 µg/g dry solids of mushrooms in 8 minutes. The conversions of ergosterol to vitamin D2 under UV-A. whose spore-producing lamellae were exposed to the sun. Under the same conditions of irradiation.5 mW/cm2 at a dose of 0.. A study has also shown that irradiating slices of Agaricus bisporus was a more efficient way of increasing the vitamin D2 content than irradiating the gill or pileus of whole mushrooms.1 µg/g d. Shiitake. 2005). 2007). wavelength 190-290nm). and Ultraviolet-C (UV-C. 20cm distance) for fresh white button mushrooms and freeze-dried chanterelles resulted in vitamin D2 increasing by up to 9-fold (Cantharellus tubaeformis) and 14-fold (A. 2008). 0–2 h. Irradiation with UV light in the A region (366nm) only slightly affected vitamin D2 content. As the irradiation doses increased. irradiation with UV light conducted in the C region (254nm. Chanterelles and king bolete were found to be good sources of vitamin D2 (0. and UV-C were shown to be significantly different.m. Button mushrooms (Agaricus bisporus). wavelength 290-315nm). wavelength 315-400nm). The generation of Vitamin D2 in edible mushrooms has been studied in fresh Shiitake mushrooms (Lentinula edodes). Raw and processed mushroom samples including wild grown (chanterelles and king bolete) and cultivated samples (white and brown button. Vitamin D is also an important factor for immune function and has been identified as a major mitigating factor in many diseases. The highest vitamin D2 content was observed in Oyster mushrooms irradiated with UV-B at 35ºC and ~80% moisture.). due to the larger exposure area. Ultraviolet-B (UV-B. Irradiation of each side of the mushrooms for 1h was found to be the optimum period of irradiation in this conversion.highest level of vitamin D was produced in Lentinus edodes. Dried mushrooms also elicited vitamin D production subsequent to sunlight exposure.5 J/cm2. bisporus/white). 2006).75µg/g dry solids of mushrooms in 18 min.) compared with cultivated mushrooms that had a low content (< 0.2µg/g d. Oyster) have been analysed for vitamin D2 content. Portabella.0 mW/cm2 at a dose of 0. the lowest vitamin D2 content was observed in button mushrooms (Jasinghe and Perera. the vitamin D2 concentration also increased for both sliced Agaricus bisporus and sliced Shiitake (Lentinus edodes) (Ko et al. and Abalone mushrooms (Pleurotus cystidus) following irradiation with Ultraviolet-A (UV-A. Canned samples of Agaricus bisporus/white were slightly lower in vitamin D2 compared to fresh samples.

Na.64mg/100g dry weight (dw). 88. Analyses of Agaricus bisporus (brown). respectively. and copper and vitamins such as riboflavin. The concentrations of minerals in Shiitake mushrooms (Lentinus edodes) are in general lower than those in the cultivated white mushroom (Agaricus bisporus) and in the Oyster mushroom (Pleurotus ostreatus). and folates. with contents varying in the ranges 1.09-0.15-7.08. Cd. and certain phenolic compounds (flavonoids.93-1038.09. The estimated volatile components comprised 18. Fe. In terms of vitamin C. 47-92mg/kg. n-nonane. Pb. K.29-238. folates. and Pleurotus ostreatus. edodes (1.2 Minerals Mushrooms contain a variety of minerals and trace elements such as potassium. while tryptophan is a limiting amino acid in some varieties (Cuptapun et al. 0. and Cu varied in the ranges 26. in three flushes and at two different harvest times showed the mean Zn. P. the content of K. and folates. benzendicarboxylic acid.0-2500. and 0.05-76. K.97. The greatest differences have been reported in the concentrations of potassium.9 g/kg. The content of mineral elements (Ca. D. Amino acid analysis has shown that protein in a variety of mushrooms contains nutritionally useful quantities of essential amino acids.29.2-554. and 3.3 g/kg. 8. respectively. strontium. 31-65. Mn.2-35mg/kg dw.407. the mean contents were 6.69. and 534. and phenolic acids) have been determined in a study of the cultivated mushrooms Agaricus bisporus/white.7-47. The total amino acid content is 15% in caps and 11% in stipes 25 .g.62-2. vitamins (B1. and niacin. 1180.80 mg/kg.75-3. lignans. Agaricus bisporus/brown. 2009). 0.30-0. No flavonoids or lignans were found in the mushrooms analysed in this study from Finland (Mattila et al.2.. Zn. 2001).2mg/kg dw). P. Mg.significant effect on vitamin D2 formation in mushrooms that were treated 1 and 4 days after harvest (Roberts et al. B2. B12.7-13.29. Cultivated mushrooms were found to be good sources of vitamin B2. copper. Cu. manganese and zinc. and niacin).1. phosphorus. respectively.2mg/kg dw) and the levels of Cd were quite high in L.94 mg/kg. 0. 4.82. hexadecanoic acid derivatives. 2008). mushrooms are a good source of many mineral elements e. Agaricus bisporus/brown was shown to contain large amounts of Se (3.. Fe. and cis-linoleic acid esters (Caglarirmak. riboflavin.7.. P. Lentinus edodes. respectively. 2010). and other important volatiles like di-limonene. niacin.or 16-carbon compounds such as octadecanoic acid. and 5. C.085-0. and Se). Na.27-0. 2652.07. Mg. The concentrations are higher in caps than in stipes. thiamin.89. folic acid. niacin. 213.8-5.96. calcium. and Ca contents of both harvests were 8. Compared with vegetables.

only because the mean life is shorter. Good bioavailablity of both copper and zinc from mycelium of Agaricus blazei Murrill equating to very good levels of recommended daily intakes of these minerals from small amounts of (1g) of this mushroom has also been reported (Rabinovich et al. Mycelia from Grifola frondosa grown in the presence of non-mycotoxic concentrations of 100 and 200 ppm (parts per million) of Cu or 25 and 50 ppm of Zn accumulated 200-322 ppm and 267-510 ppm of Cu or Zn. cultivated species accumulate lower levels than wild mushroom species. 2010).3mg Zn/kg) for Cu and Zn. When the enriched metal mycelia were subjected to a simulated gastrointestinal digestion in vitro. Gly. 2007). Some mushrooms can bioaccumulate undesirable levels of compounds such as mercury (Alonso et al. Cantharellus cibarius. were bioexclusors. with the authors discussing potential uses of the mineral-enriched mycelia in capsules (in the case of Cu-enriched mycelia) and in food preparations (Figlas et al. 2003). 1995).0mg Zn/kg). which represent approximately 32-33% and 0.. with the authors concluding that the consumption of these mushrooms cannot be considered a toxicological risk. Macrolepiota procera (217. respectively. His. high-quality products (e. All mushroom species bioaccumulated copper and zinc. Arg.(dry matter)... The hymenophore in mushrooms showed higher mean levels than the rest of the fruit bodies. while some individual samples of the species.7mg Cu/kg) and Calvatia utriformis (265. Agaricus macrosporus (217. In this study.5% of the recommended daily intake (RDI) for Cu and Zn. such as Hydnum repandum. 1990) when grown in polluted ecosystems. in 1 g of mycelium. In such environments. with statistically significant differences.8mg Cu/kg). and Agaricus macrosporus (221. respectively. and that they provide an important nutritional requirement to the diet (Alonso et al. The possibility of utilizing agro-industrial wastes in the production of edible.. 26 .g. The amounts of the amino acids Phe. the copper and zinc concentrations were compared to literature data and levels set by legislation. Ile and Met are relatively higher than in Agaricus fruit bodies (Vetter.7-3. respectively.8mg Zn/kg).. 2000) and cadmium (Favero et al. such as heavy metals.5mg Cu/kg). the solubility in the digestive fluids was 642-669 ppm and 102-530 ppm. A study on the copper and zinc contents of 28 species of edible mushrooms (from different sites in NW Spain) has shown that the element concentrations were species-dependent. with the highest levels corresponding to the following species: Calvatia utriformis (235. into the human food chain. and Coprinus comatus. mushrooms) implies the risk of bringing toxic substances. Lactarius delicious (231..

and several unidentified selenocompounds (Falandysz. 2010). It has been shown that Pleurotus cornucopiae (Paulet) Rolland and Grifola frondosa (Dicks.. 2008). Furthermore. Selenium increased in basidiomata of both mushrooms in direct response to levels added to the substrate.2. 2009).2. 2006). The average cap/stipe Se ratio has been reported to be 1. superoxide dismutase (SOD) and a decrease in malondialdehyde (MDA) (Song et al.) S. and the changes of Se concentration during cultivation (in cultivation's flushes) are not significant (Vetter and Lelley. but greater uptake of selenium occurred with P. 2010a). selenite. Gray mushrooms are able to be enriched with selenium by addition of sodium selenite to the growth substrate.. Se-methylselenocysteine. 27 .1 Selenium Selenium (Se) levels in humans are very dependent on the Se-content of consumed food. lucidum in the form of selenocysteine and selenomethionine.:Fr. The main subsistent forms of selenium in Se-enriched mycelia are selenoproteins and selenium-polysaccharides and Se enrichment studies in mushrooms have also reported an elevation of glutathione peroxidase (GSH-Px). cornucopiae compared to G. selenomethionine..F. The selenium content of different.4. frondosa. 2004). An increasingly growing database on chemical forms of selenium of mushrooms indicates that the seleno-compounds include selenocysteine. common varieties of Agaricus bisporus is very high. The results indicated that both mushrooms can be predictably enriched with selenium to become an excellent nutritional source of selenium (Beelman and Royse. and the caps of fruit bodies have a higher Se content than the stipe. Selenium in selenium-enriched Pleurotus ostreatus has been shown to be highly bioavailable in a study in Wistar rats (da Silva et al. may contribute to their antitumor activity (Du et al. it has been proposed that the immune-regulatory activity and selenium-containing attribute of proteins from Ganoderma lucidum or selenium-enriched G. A higher intake of selenium can decrease the risk of a number of health problems.29.

in vitro and animal trials have reported an inhibition of aromatase activity and subsequent reduction of estrogen by mushroom extracts. although only a conference abstract is currently available. the growing data suggest that the mushrooms and mushroom extracts tested in humans are safe and generally well-tolerated. and therefore. In addition to the studies in human population groups and human cell lines provided in Table 1. However.5. double-blind. Effects of mushrooms and mushroom components on health 5. A decrease in aromatase activity has also recently been demonstrated in a human trial following consumption of Agaricus bisporus (Palomares et al. the effects need to be confirmed via intervention trials involving mushroom consumption. placebo controlled human studies have recently been completed and several others are in progress. Preliminary new data showing protective effects of mushrooms on beta-amyloid peptide toxicity in the brain and mild cognitive impairment (both precursors to dementia) are promising and warrant further research on the ability of mushroom consumption to delay the onset of cognitive decline / Alzheimer’s disease.. The most promising data appear to be those indicating an inverse relationship between mushroom consumption and breast cancer risk. the properties and mechanisms of bioactive compounds and mushroom extracts evaluated in animal models or animal cell lines are provided in Table 8. 28 . which provide a physiologically-relevant mechanism for effects on estrogen receptor positive tumors. although most of the studies to date are based on food frequency /diet recalls. The human trials carried out to date have primarily been smaller observational studies. 2011). In general. which can be affected by recall bias.1 Studies in Humans The properties and mechanisms of extracts and bioactive compounds from mushrooms that have been evaluated in a human population or human cell lines are outlined in Table 7. although larger.

Table  7:  Properties  and  mechanisms  of  bioactive  compounds  and  mushroom  extracts  evaluated  in  a  human  population  or  human  cell  lines   BIOACTIVE  or  EXTRACT   MUSHROOM  VARIETY   MECHANISM   REFERENCE   (in  vitro/  in  vivo)             Anti-­‐Cancer  (Breast)   Ergosterol   Unspecified  variety   Increase  serum  25  (OH)  vitamin  D2  levels  (in  vivo-­‐ Furlanetto  2009   humans)   Aqueous  extracts   Agaricus  bisporus   Suppress  aromatase  activity  and  proliferation  of   Grube  et  al  2001   EFFECT/  DISEASE   STATE     Hydroxylated  triterpenes     Multiple  varieties   Polysaccharopeptides     Ganerderma  lucidum   Anti-­‐Cancer   (Colorectal)   Trametes  versicolor    (Tv)   Polysaccharide  extract   Coriolus  versicolor   YUNZHI-­‐BC   Unspecified  extract   Unspecified  extract   Polysaccharide  K    (PSK)(in   adjunct  with  immuno-­‐ chemotherapy)   Unspecified  bioactive/   extract   Lectin   Yunzhi   Unspecified  bioactive/   extract   Ganoderma  lucidum   Aqueous  extract   Inonotus  obliquus   Agaricus  bisporus   Coriolus  versicolor  CM-­‐10   Agaricus  sylvaticus   Agaricus  bisporus  (ABL)   MCF-­‐7aro  cells-­‐  hence  suggesting  a  reduction  in   oestrogen  production  (breast  cancer  cell  lines)   Downregulation  of  Akt/NF-­‐kappaB  signalling   Apoptosis  (human  cell  lines)   Suppress  oxidative  stress  stimulated   phosphorylation  of  Erk1/2  resulting  in   downregulation  of  expression  of  c-­‐fos  &  inhibition   of  transcription  factors  AP-­‐1  and  NF-­‐kappaB   Phase  1  trial  studying  the  side  effects.  Sakamoto   et  al  2006   Fortes  et  al  2009     Yu  et  al  1993   Hong  et  al  2004   Lee  et  al  2009b   .5g/  day  of  YUNZHI-­‐BC  as  a  dietary   supplement    for  breast  cancer  patients   Decrease  of  aroamatase  activity   Stimulate  both  innate  and  adaptive  immune   pathways    in  curatively  resected  colorectal  cancer   (in  vivo)   Benefits  in  haematological  and  immunological   parameters  &  reduction  in  glycemic  levels  (in  vivo)   Inhibit  the  proliferation  of  HT29  human  colonic   cells  (in  vitro  -­‐in  human  cells)   Apoptosis  (induced  by  increase  in  caspase-­‐3   activity)  &  Anti-­‐inflammatory  function  in  HT-­‐29  in   human  carcinoma  cells  (no  toxicity  in  HT-­‐29  cells   in  doses  <10mg/ml)  (in  vivo)   Apoptosis  and  inhibition  of  the  growth  of  HT-­‐29   Jiang  et  al  2008   Wan  et  al  2008   Thyagarajan  et  al  2006   NCT00680667   Completed*   NCT00647075   Status  unknown   Palomares  et  al  2011   Oba  et  al  2007.  tolerability   and  best  dose  (clinical  trial  first  registered  2008)     Effect  of  3.

2010). double-blind trials to assess the efficacy of Yun Zhi (YZ) for survival in cancer patients has recently been published. including Agaricus bisporus. The effects of Active Hexose Correlated Compound (AHCC) from Lentinula edodes (Shah et al. The meta-analysis has provided strong evidence that Yun Zhi would have survival benefit in cancer patients. gastric and colorectal cancer (Eliza et al. primarily in human cell lines. a number of human trials have been undertaken and these are outlined below. Oyster 39 . but not in esophageal cancer and nasophayngeal carcinoma. 2011). have been reported for polysaccharides extracted from various mushrooms. The polysaccharides generally belong to the beta-glucan family of compounds and appear to exert their anti-tumorigenic effects via enhancement of cellular immunity. gastric cancer. had a 9% absolute reduction in 5-year mortality. as have the anti-cancer properties of five commonlyconsumed edible mushrooms: button mushrooms (Agaricus bisporus). 2011) and the use of Phellinus linteus as complementary therapies in patients with cancer have been reviewed (Sliva. involve the elevation of natural killer (NK) cell numbers and the stimulation of inducible nitric oxide (NO) synthase gene expression.. While studies in human cell lines provide supporting evidence. A small pilot study of 7 patients undergoing post-operative cancer chemotherapy has reported that the concomitant administration of Lentinula edodes mycelia extract with chemotherapy is safe and improves the quality of life and immune function of patients. which is then followed by NO production in macrophages via activation of the transcription factor. Activation of NK cells is likely via interferon-gamma and interleukin mediated pathways. although these potential effects remain to be confirmed by larger trials (Yamaguchi et al.1. Patients randomized to Yun Zhi. subgroup analysis could not conclude which type of anticancer treatment may maximize the benefit from Yun Zhi. However. A systematic review and meta-analysis of randomized.. In recent years.. particularly in patients with carcinoma of the breast. well-designed human clinical trials are required before anti-cancer health outcomes in humans can be validated. 2012). Thirteen clinical trials were evaluated with the data showing that Yun Zhi resulted in a significant survival advantage compared with standard conventional anti-cancer treatment alone. the effects of the combination of Yun Zhi preparation on the overall 5-year survival rate was more evident. or colorectal cancer treated with chemotherapy. NF-kappaB. resulting in one additional patient alive for every 11 patients treated.1 Anti-Cancer Studies Anti-tumor effects. A. blazei.5. Anti-tumor effects of proteoglycan fractions from a variety of mushrooms. In patients with breast cancer. placebo-controlled.

nrv. AI (Adequate Intake) -used when an RDI cannot be determined The average daily nutrient intake level based on observed or experimentally-determined approximations or estimates of nutrient intake by a group (or groups) of apparently healthy people that are assumed to be adequate.au % RDI = an average of the international figures on Agaricus bisporus NA = Not available Mushroom information (spelling. Appendix – Compositional tables: Raw. RDI/ AIs Taken from Nutrient Reference Values for Australia and New Zealand (2006) Available at http://www. names and species) has been entered into the tables exactly as they are shown in references sources.Notes on Nutrient Tables RDI (Recommended Dietary Intake) The average daily dietary intake level that is sufficient to meet the nutrient requirements of nearly all (97–98 per cent) healthy individuals in a particular life stage and gender group.gov. No attempt has been made to standardize them.27. Cooked and Dried Mushrooms Mushroom Nutrient Summary . .

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(This edition compiled by Scherz.... P.com/facts&nutrition. and some phenolic compounds in cultivated mushrooms.. Aro. Jalava. Fachmann. H. Eurola. H.Med Pharm and CRC Press. T. P. 1994. Mattila. Agricultural Research Service Nutrient Data Laboratory.. H and Senser.. 2011. Huetaniemi.. M. 50: 6419-6422. Log Grown.) (USDA) U.. 2012.S. J Agric Food Chem 2002.. Kumpulainen. Release 24.gov/ba/bhnrc/ndl Accessed 24 May.usda.. W. Pihalva..-5th ed – Stuttgart . Department of Agriculture. 253 . J Agric Food Chem 2001 49: 2343-2348. mineral elements. Basic composition and amino acid contents of mushrooms cultivated in Finland.Mattila.html (Actual source of calculations not given) Accessed on 23 May. USDA National Nutrient Database for Standard Reference. J-M. S. Valtonen. M and Piironen. J. Astola. http://www.. Available at Nutrient Data Laboratory Home Page. Konko. Salo-Vaananen. V. V. Konko. K. 2012.W. P. Data from http://shiitakemushroomlog.ars. and Kraut. F. J.. K. L. Food Composition and Nutrition tables. Vahterist. (Ger) Souci. Contents of vitamins.

5% 40.9% 25.5% 37.5% 30.39 30.1 38.0% Nutrient Mushrooms white Agaricus bisporus (USDA) Mushrooms common (UK) India (Goyal 2006) Champignon fresh A.3 1.4% 20.8% 10.9% 44 13.0% 3.1% 33.13 10.2% 41 0.49 37.19 0.2% 23.7% 3.6% 29.0% 4.72 23.44 33.1% 22 0.Summary Tables for RAW COMMON MUSHROOMS (Agaricus bisporus) providing >10% RDI/AI of key vitamins/100g Riboflavin (B2) (mg) Males 19-70 years Males over 70 years Females 19-70 years Females over 70 years Niacin equivalents (B3) (mg) Males 19 years and over Females 19 years and over Folate (mcg) Males 19 years and over Females 19 years and over Vit B6 (mg) Males 19-50 years Males over 50 years Females 19-50 years Females over 50 years RDI 1.4% 254 .8 23.05 37.5% 11.02 26.31 23.4% 4.8 23.8% 27. raw (Can) Mushroom Brown Italian or Crimini raw Agaricus bisporus (USDA) Mushroom Brown Italian (Crimini) raw (Can) Mushroom Portabella exposed to UV light raw A.8% 17 0.3% 3 18.0% 33.4% 11.3 20.9% 16 0.3% 38.8% 27.0% 33.1% 43.8% 0.7% 30.5% 28.5% 30.1% 14 0.4% 44.3 RDI 16 14 RDI 400 400 RDI 1.5% N/A 0.402 30.8% 3.0% 11.7 1.6% 30.0% 11.0% 0.0% 22.3% 10.8% 6.1% 32. white. bisporus (USDA) N/A N/A N/A 11.06 N/A 0.8% 27.3 1.6% 0.9% 4.5% 30.4% 11.8% 10.065 26.6% 23.4% 11.9% 3.4% 28.0% 10.4% 22.0% 11.3% 18.6 1.0% 24.1% 36.1% 32. raw (Can) Mushroom Portabella raw Agaricus bisporus (USDA) Mushroom Portabella (Portobello).6% 35 0.2% 32.494 28.1% 25 0.4% 10.8% 12.148 11.1% 28 0.0% 13. bisporus (Fin) Common mushroom (Jap) Mushroom Agaricus bisporus (Den) Mushroom Agaricus bisporus SFK (Ger) Mushroom Common Agaricus bisporus (Aust) Mushroom.3% 0.1 25.8% 27.148 11.44 33.7% 30.3 1.4% 35.3% 0.42 32.8% 10.4% 28 0.5% 37.607 22.7% 3.18 N/A N/A 0.1% 26.369 28.1 1.3% 6.6% 18 0.3% 46 0.104 4.2 20.49 37.11 0.8% 12.5% 25.402 30.4% 23.148 11.1% 32.5% 40.29 22.11 11.6% 13.104 11.6% 13.8% 19.1% 36.1% 28 0.8% 43.13 10.9% 25.2% 29.6% 0.13 10.8% 21.33 25.18 0.494 28.4% 3.8% 10.11 44.0% 4.0% 0.8% N/A 0.6% 36 Agariscus bisporus brown (Matilla 2002) 0.5 Agariscus bisporus white (Matilla 2002) 0.0% 25.3% 26.494 28.

1 35.0% 28.7% 38.175 1.7% Nutrient Agariscus bisporus white (Matilla 2002) N/A N/A N/A N/A Agariscus bisporus brown (Matilla 2002) N/A N/A N/A N/A 2.3 0. white.0% 10.0% 28.4% 12.9% 224. bisporus (Fin) Common mushroom (Jap) Mushroom Agaricus bisporus (Den) 1.2 1 N/A Mushrooms white Agaricus bisporus (USDA) Mushrooms common (UK) India (Goyal 2006) 1.6% 1 N/A 1.2% 28.0% 28.0% 16 53.1 Mushroom Brown Italian (Crimini) raw (Can) 1.0% 52.5% N/A 0 11.7% 35.Summary Table for RAW COMMON MUSHROOMS (Agaricus bisporus) providing >10% RDI/AI of key vitamins/100g Pantothenic acid (mg) Males 19 years and over Females 19 years and over Biotin (mcg) Males 19 years and over Females 19 years and over Vit C (mg) Males 19 years and over Females 19 years and over Vit D (mcg) Males 19-50 years Males 51-70 years Males over 70 years Females 19-50 years Females 51-70 years Females over 70 years AI 6 4 AI 30 25 RDI 45 45 AI 5 10 15 5 10 15 20. bisporus (USDA) 1.5% N/A 0 0.5% N/A 0 0.497 25.8% 8.3% 50.14 19.5% N/A 2 33.9% 1.7% 224.14 19.1 0.1 Mushroom Portabella exposed to UV light raw A.0% 20.0% 74.14 19.0% 37.4% N/A 2 33.0% 37.3 Mushroom Portabella (Portobello).4% 12.0% 37.9% 38.5% 16 53.0% N/A N/A N/A N/A N/A N/A 1.9 29.0% 3.5% N/A 0 0.0% 112.0% 112.2 Mushroom.4% N/A 2.8% 19.497 25.9 Mushroom Common Agaricus bisporus (Aust) 1.8% 19.3 Mushroom Brown Italian or Crimini raw Agaricus bisporus (USDA) 1. raw (Can) Mushroom Portabella raw Agaricus bisporus (USDA) 255 10.1 Mushroom Agaricus bisporus SFK (Ger) 2.0% 10.15 19.3% 50.3% 64.0% 48.54 25.0% 38.5% N/A 0 0.5 25.0% 4.3% 64. raw (Can) 1.0% 37.0% 74.1 0.0% 12 40.2 1 1 0 Champignon fresh A.5 25.9% 10.94 .

Bisporus.3-11.5% Agaricus bisporus brown (Matilla 2002) providing the greatest amount #>10% RDI provided by 5 of the 16 for M and F • Range male 19 and over – 10.9% Mushroom Agaricus Bisporus SFK (Ger) 5mcg Male and female 19-50: 10mcg male and female 51-70: 15mcg male and female >70 # >10% AI provided by 3 of 16 mushrooms for M and F • Range male and female 19 – 50: 20–224% • Range male and female 51-70: 10–112% • Range male and female 70 and over: 12.6% Champignion Fresh (A.3mg male 19-7 : 1.5% Mushroom Brown Italian (Crimini) Raw (USDA) and (Can) providing the greatest amount #>10% RDI Provided for 14 of 16 for M and F • Range male 19 and over – 18. bisporus (USDA) providing the greatest amount at 11.1% • Range female 19 and over – 21.6 -64% Mushroom agaricus bisporaus (Den) and Mushroom Agaricus Bisporus SFK (Ger) providing the greatest amount #>10% RDI provided by 1 of 14 mushrooms for M and F • 10.5-52.6 -13.4-13.9% 30mg male 19 and over 25mg female 19 and over Vitamin C M and F 10.Bisporus) (Fin) providing the greatest amount # >10%RDI provided by 3 of 16 mushrooms for M and F • Range male and female 19 and over – 10.8% Mushroom common (UK) and Champignion Fresh (A.7% • Range female 19 and over – 10-44.3% F 37.9% M and F 64% 45mg male and female 19 and over Vitamin D 24 Comments # > 10% RDI Provided by 15 of 16 mushrooms for M and F • Range male 19 and over – 10-37.3% • Range female 19 and over – 35.8% F 28.6mg men>70 1.Table 1 Average24 %RDI/AI content for each Key Vitamin /100g Vitamin Average % Recommended Dietary Intake Riboflavin (B2) M 25.9-74.9% 400mcg male and female 19 and over Vitamin B6 M 11.9% 6mg male 19 and over 4mg female 19 and over Biotin M 44.1mg Female 19-70:1.5% Mushroom Agaricus bisporus SFK (Ger) providing the greatest amount #>10% AI provided by 4 of the 16 for M and F • Range male 19 and over – 29.1% F 52.8% • Range female 19 and over – 11.3 Females 19-50 : 1.9% 1.2mcg/100g Average values taken from mushroom data providing greater than or equal to 10%RDI/AI 256 .9% F 12.8-38.7mg male >70 1.3mg female>70 Niacin (B3) M 26% F 29. (Fin) providing the greatest amount #>10% AI provided by 12 of the 16 for M and F • Range male 19 and over – 19 – 35% • Range female 19 and over – 28.4-43.8% 16mg male 19 and over 14mg female 19 and over Folate M and F 10.3mg male 19-50 yrs : 1.7% Mushroom Portabella exposed to UV light raw A.5 female > 50 years Pantothenic acid M 25.7 – 53.3% 1.

8% 10.4% 41.318 18.5% 125 12.8% 10.0% 257 10.1% 28.0% .0% 448 11.7% 26.0% 11.9% 13.5% 363 13.4% 60.0% 0.5 29.5% Mushrooms common (UK) 0.5% 86 318 11.1% 10.8% 16.0% 359 12.8% 108 10.318 18.286 16.3% 98 Agariscus bisporus brown (Matilla 2002) 0.286 16.7 1.8% 23.0% 310 11.0% India (Goyal 2006) Champignon fresh A.7% 120 12.8% 108 10. raw (Can) Mushroom Brown Italian or Crimini raw Agaricus bisporus (USDA) Mushroom Brown Italian (Crimini) raw (Can) Mushroom Portabella exposed to UV light raw A. bisporus (USDA) 364 13.22 12.0% 11.1% Mushroom.0% 0. white. raw (Can) 0.8% 23.8% 364 Nutrient Mushroom Agaricus bisporus (Den) Mushroom Agaricus bisporus SFK (Ger) Mushroom Portabella (Portobello).2 RDI 1000 1000 AI 3800 2800 Agariscus bisporus white (Matilla 2002) 0.7% 100 0.0% 0. bisporus (Fin) Common mushroom (Jap) 0.0% 85.342 20.5% 12.8% 86 318 11.8% 26.8% 364 13.39 22.32 18.4% Mushroom Portabella raw Agaricus bisporus (USDA) 0.9% 32.0% 10.8% 108 10.4% N/A N/A N/A N/A 98 364 13.5% 110 11.8% 16.4% 41.7% 26.Summary Table for RAW COMMON MUSHROOMS (Agaricus bisporus) providing >10% RDI/AI of key minerals /100g Copper (mg) Males 19 years and over Females 19 years and over Phosphorus (mg) Males 19 years and over Females 19 years and over Potassium (mg) Males 19 years and over Females 19 years and over AI 1.42 24.4% 80 320 11.72 42.1% 10.8% 10.5% 417 Mushroom Common Agaricus bisporus (Aust) 0.7% 120 12.27 15.1 0.5 29.9% 18.0% 14.0% 12.0% 350 12.0% 448 11.0% 0.9% 22.0% 12.5% 101 Mushrooms white Agaricus bisporus (USDA) 0.286 16.8% 23.8% 364 13.7% 35.

9% .56 0.31 Nutrient India (Goyal 2006) N/A Champignon fresh A.5 0.54 1.47 18.31 258 14.1% 43.7% 6.7% 0.53 Mushroom Portabella (Portobello).4 18.53 0.1 13.6% 31.27 Mushroom.6 26.7% 0.31 26 37.3 13.4 0.6 26.4 0.4 0. white.3% 7.3% 1.0% 25.9% 14.5% 0.0% 0.31 18.19 Mushroom Common Agaricus bisporus (Aust) 15.0% 11.3 10. raw (Can) 9.1 13. raw (Can) Mushroom Brown Italian or Crimini raw Agaricus bisporus (USDA) Mushroom Brown Italian (Crimini) raw (Can) Mushroom Portabella exposed to UV light raw A.6 26.6 N/A N/A 0.5% 0. bisporus (USDA) 0.8% 0.5 Mushroom Portabella raw Agaricus bisporus (USDA) 18.3% 15.Summary Table for RAW COMMON MUSHROOMS (Agaricus bisporus) providing >10% RDI/AI of key minerals /100g Selenium (mcg) Males 19 years and over Females 19 years and over Zinc (mg) Males 19 years and over Females 19 years and over Iron (mg) Males 19 years and over Females 19-50 years Females over 50 years RDI 70 60 RDI 14 8 RDI 8 18 8 Agariscus bisporus white (Matilla 2002) 11 15.0% 0.48 0.8% 0.4 26 37.6% 31.52 0.4 22.7% 41. bisporus (Fin) 11 Common mushroom (Jap) N/A Mushroom Agaricus bisporus (Den) Mushroom Agaricus bisporus SFK (Ger) 15.6% 31.0% 0.3% N/A N/A Agariscus bisporus brown (Matilla 2002) 25 35.5 Mushrooms common (UK) 9 12.3% 1.02 10.53 0.3 13.8% 0.52 0.7% 18.0% 0.1% 43.3% 15.7% N/A N/A Mushrooms white Agaricus bisporus (USDA) 9.9% 15.

common (UK) Providing the greatest amount # >10% RDI provided by 9 of 16 mushrooms for M and F • Range male and female 19 and over – 10-12.8% • Range female 19 and over – 11.8% only 14mg male 19 and over 8mg females 19 and over Iron M and F (over 50) 14.3% Mushroom Brown Italian or Crimini raw Agaricus bisporus (UDSA) and (Can) providing the greatest amount Zinc F 13.1% 1000mg male 19 and over 1000mg Female 19 and over Potassium M 11.9 % # >10% AI provided by 14 of 16 mushrooms for M and F • Range male 19 and over – 12.5% F 13% 3800 mg male 19 and over 2800mg female 19 and over Selenium M 22.7% F 30.2mg female 19 and over Phosphorous M and F 11.4% • Range female 19 and over – 18.9.1-16% Mushroom Brown Italian or Crimini raw Agaricus bisporus (UDSA) and (Can) at 11.7mg male 19 and over 1.5% F 25.42.5% Mushroom Agaricus Bisporus SFK (Ger) providing the greatest amount # >10% AI provided by M 3 and F 15 of 16 Mushrooms • Range male 19 and over – 11-11.Table2 Average %RDI/AI content for each Key MINERAL /100g Mineral Average % Recommended Dietary Intake Comments Copper M 21.3 -60% Mushrooms .8% 1.8%-43.9% only 8mg male 19 and over 18mg females 19-50 and over 8mg females over 50 # >10% RDI provided by 2 of 16 Mushrooms for Females 19 years : Mushroom Brown Italian or Crimini raw Agaricus bisporus (UDSA) and (Can) # >10% RDI provided by 1 of 16 mushrooms Mushroom Agaricus bisporus SFK (Ger) at 14.8% providing the greatest amount 259 .2% 70mcg male 19 and over 60mcg female 19 and over # >10% RDI provided by 13 of 16 mushrooms for M and F • Male 19 and over – 10% – 37.1% • Female 19 and over – 10.

3 33/138 2 2.6 Oyster (USDA) 3.3% 14.1 Oyster (Jap) 3.0% 34/142 12.2 6 Mushroom Boletus.8 12.0% 41/172 28/116 20. raw (Jap) 6.8 1.9 18/75 Milk-cap Northern (Fin) 2.7% 15.7% 14.8% 18/75 4.6 Oyster.4% 20/84 20.2% 23/96 10.0% 13.5 21/89 Oyster Pleurotus spp SFKGer 2.5 Shimej Bunashimeji (Jap) 2.35 5.7 Oyster.8 3.0% 19.2% 27/111 Shiitake (Log grown) 1.Summary Table for RAW CULINARY SPECIALTY MUSHROOMS providing >10% AI for protein and fibre /100g Protein (g) Males 19-70 years Males over 70 years Females 19-70 years Females over 70 years Fibre (g) Males 19 years and over Females 19 years and over Energy (kcal/kj) RDI 64 81 46 57 AI 30 25 RDI 3 3. Usuhiratake.3 14.0% 24.7 3.2% 24/100 3.4 26/110 Boletus edible (Fin) 3. Russula (Fin) 1.1 1.3% 10.85 Nutrient Shiitake Nama-shiitake (Jap) Oyster Pleurotte (Fin) 13.0% 18/75 Shiitake dong gwoo (Fin) 1.4% 17/73 10/45 .3% 17.3 11.5% 24.5 0.24 2.5 11.6 Mushroom shiitake raw Lentinus edodes (USDA) 2.8 1. raw (Jap) 3.31 2. Eringii.3 2.9 Chantarelle (Fin) 1.8 6 False Morel (Fin) 1.7% 260 N/A 10.0% 23.

7% 15.7 3.3 Enoki (USDA) 2.8% Matsutake.8% Maitake (USDA) 1.6 3.8 Morel.7 Yanagimatsutake.Summary Table for RAW CULINARY SPECIALTY MUSHROOMS providing >10% AI for protein and fibre /100g continued Protein (g) Males 19-70 years Males over 70 years Females 19-70 years Females over 70 years Fibre (g) Males 19 years and over Females 19 years and over RDI 64 81 46 57 AI 30 25 Nutrient Mushroom Oyster.0% 10.8 11. raw (USDA) 1. raw (Jap) 3. raw (Jap) • 25 25 10. raw (Jap) 3.8% Winter Mushrooms (Jap) 2.1 3.3 % of the AI for fibre for both male and females aged 19 years and over whereas the common variety mushroom provides an average of 5.7 15.0% 13.12 2.1 3. raw (Can) 3.0% Shimeji Honshimeji.7 2.66 2. raw (Jap) 3.4 3 10.7 10.8% 12.7 Chanterelle.2% Maitake. raw (Jap) 3.7 10. raw (Jap) 2.31 2.2% Numeisugitake. raw (Jap) 2.2% 100g of fresh culinary specialty mushrooms provide an average of 12.0% 13. raw (Can) 1.8% 10. raw (USDA) 3.0% Kuroawabitake.49 3. raw (Jap) 1.8% Mushroom Enoki.7% 14.3 11.7 4.7 3.4% 2 4.2% Shimeji Hatakeshimeji.0% 13.1 13. raw (Jap) 2.0% 15.7 10.9 13.3 11.2% Maitake.7% 16.5 11. raw (Can) 2.5% AI for fibre males 19yeas and over equals 30g and for females 19 years and over equals 25g 261 .56 2.5 Tamogitake.0% 12.7% 18.94 2.3 11.94 2.6% Nameko.3 2.

4% 30.4 33.191 15.5% 8.3% 36.5% 10.4% 11.3% 31. Eringii.015 0.3% 10.1% 32.9 43.887 24.5% 8.5% 60.1% 21 False Morel (Fin) 0.9% 17.1% 21 Milk-cap Northern (Fin) 0.9 36.2% 32.2 15.1 0.0% Oyster (Jap) 0.7% 16.5% 23.3% 6.0% 36.3 25.4% 30.7% 26.5% 12.5% 37.4 52.16 13.41 31.8% 25.5% Shiitake (Log grown) 0.8% 5.07 0.4% 12.03 0.0% 36.1 50.5% 17.4% 38 Oyster Pleurotte (Fin) 0.3% 38.6% 37.4 30.4 30.4% 0.0% Oyster.4 30.3% 47.1 RDI 1.0% 14.5% 0.14 11.1 38.1 0.3% 18.9% 17.3% 0.5% 13.4% 0.1 0.8% 5.6% 11.3% 100 25.8% 5.5% 6.0% 35 Mushroom Boletus.9% 42.1% 43.3% 6.15 11.0% 36.6% 25 Shiitake Nama-shiitake (Jap) 0.1 0.1% 49.1% 42 10.8% 13 Mushroom shiitake raw Lentinus edodes (USDA) Shimej Bunashimeji (Jap) 33.217 16.8% 12.5% 25.28 21.3 1.9% 0.0% 36.7% 3.1% 51 12.5% 2. raw (Jap) 0.8% 4.6% Shiitake dong gwoo (Fin) 0.6 41.4 0.4% 262 N/A .0% 36.2 1.0% 35.1 Oyster Pleurotus spp SFK-Ger 0.5% 18.37 28.8% 25.5 28.3 RDI 16 14 RDI 400 400 11.5 Chantarelle (Fin) 0.3% 27.3% 36.3% 14.5% 25.7% 0.8% 27. Usuhiratake.0% 25.8% 10.8% 25.6% 35 0.9% 21.8% 25.4% 30.0% 27.6% 19.4% 30.9% 42.8% 4.4% 92 23.16 12.4% 5.42 32.9% 80 20.6% 57.285 21.7% 12.2 32.125 10.7 66.8% 31.1 1.6% 3.9% 42.4 30.6 16.1% 28 Oyster.6 1.9 36.19 14.9% 76.8% 25.349 26.0% Oyster (USDA) 0.0% 23.4 30.Summary Table for RAW CULINARY SPECIALTY MUSHROOMS providing >10% RDI/AI of key vitamins /100g Nutrient Thiamin (B1) (mg) Males 19 years and over Females 19 years and over Riboflavin (B2) (mg) Males 19-70 years Males over 70 years Females 19-70 years Females over 70 years Niacin equivalents (B3) (mg) Males 19 years and over Females 19 years and over Folate (mcg) Males 19 years and over Females 19 years and over RDI 1.1 0.8 23.8% 25.1% 25.8% Boletus edible (Fin) 0.05 0.4% 0.3% 14.7% 13.9% 17.0% 20.5% 21.1% 33.4% 30.8% 21.6% 28.9 36.3% 26.2% 15. raw (Jap) 0.956 31. Russula (Fin) 0.1% N/A 0.

6% 30.6% 15.5% 0.5% 31. raw (Can) 0.242 18.5% 13.12 0. raw (USDA) 0.5% 10.1% 63 15.2% 6.5% 0. raw (Jap) Kuroawabitake.6 1.49 37.1% 10.2% 47.069 0.585 41.162 12.1% 0.1% 43.5% 18.032 44.015 0.25 20.3% 16.4% 20.8% 0.7% 6.5% 4.8% 45.3% 14.2% 5.7% 0.5% 16.125 10.1% 22. raw (Jap) Matsutake.17 14.34 26.2% 21.179 14.0% 12.9% 26.1% 14.3% 30.22 16.1 38.49 37.12 10. raw (Jap) 0.0% 25. raw (Can) 0. raw (Jap) Numeisugitake.6% 75 18.2% 15.456 0.8% 22.8% 20.5% 9 56.3% 13.0% Mushroom Enoki.1% 16.6% 15.1% 9 Maitake. raw (Jap) 0.6% 15.9 36.5% 19.7% 65 16.4% 0.5% 0.8% 0.0% 50.7% 30.8% Nameko.9% 26.8% 20.Summary Table for RAW CULINARY SPECIALTY MUSHROOMS providing >10% RDI/AI of key vitamins /100g continued Nutrient Thiamin (B1) (mg) Males 19 years and over Females 19 years and over Riboflavin (B2) (mg) Males 19-70 years Males over 70 years Females 19-70 years Females over 70 years Niacin equivalents (B3) (mg) Males 19 years and over Females 19 years and over Folate (mcg) Males 19 years and over Females 19 years and over 1.17 13.7% 80 0.1% 43.3% 38 20.4% 19.0% 10.6% 25 0.16 13.0% 21.085 25.2% 13.1 31.4% 12.6% 44.3 RDI 16 14 RDI 400 400 RDI 1.8% 12.5% Maitake.4% 11.9% 2.0% 13.8% 18. raw (USDA) 0.6% 33 0.3 1.1 1.8% 2.6% 6.1 56.3% 64.1 12.3% 0.5% 6.205 15.5% 37.3% 30.3% 8 50.8 42. raw (Jap) 5.0% 20.0% 57.8% 15.1 RDI Mushroom Oyster.4% 7.5% 29. raw (Jap) Shimeji Hatakeshimeji. raw (Jap) Shimeji Honshimeji.5 38.3% 263 .2% 2 Morel.2% 48 12.2% 0.34 26.2 1.5% 52 13. raw (Can) 0.252 14.9% 27 0.215 16.1% 22.5% 13.6% 29 12.0% 18.2% 21.9% 16.372 39.0% 0.5% 24.3% 45.24 20.4% 12 75.9% 65.9% 42.242 18.1 Maitake (USDA) 0.0% 85.9% 36.2% 15.2 15.27 22.146 Chanterelle.5% 48.0% 16.4% 49.33 25.7% 12.0% Winter Mushrooms (Jap) 0.225 18.4% 58 14.6% 15.9% 0.08 10.9 18.5% 37.0% 15.0% Yanagimatsutake.7% 9.146 0.5% 38.1% 6.9% 13.0% 60 15. raw (Jap) Tamogitake.8% 18.21 17.1% 19 0.6% 44.07 5.7% 30.0% 21 0.1% 20.5% 14.6% 6.0% 18.1 38.349 Enoki (USDA) 0.941 43.5% 0.

8% 10.0% N/A Oyster Pleurotus spp SFK-Ger 0.9% 16.0% 1. Eringii.0% 27.7% N/A 22.3 1.294 21.5% Shiitake Nama-shiitake (Jap) 0.7% N/A Milk-cap Northern (Fin) 0.7% 15. raw (Jap) 0.0% 1.8% 40.08 Shiitake dong gwoo (Fin) N/A N/A Shiitake (Log grown) N/A N/A Mushroom shiitake raw Lentinus edodes (USDA) 0.3 1.293 Shimej Bunashimeji (Jap) 0.44 40. Usuhiratake.5% 17. Russula (Fin) 0.08 Oyster.2% 22.18 13.4 40.7% 51.22 16.8% 12.61 26.7% 13.18 13.6% 13.0% Oyster (Jap) 0.0% 60.9% 14.9% 12.4% Oyster Pleurotte (Fin) N/A N/A Boletus edible (Fin) 0.7% 61.5% 19.9% 14.8% 10.0% Oyster (USDA) 0.7% 58.7% N/A Chantarelle (Fin) 0.5% N/A 264 .22 16.88 67.23 17.5% 17.3% 21.11 1.5 AI 6 4 18.8% 12.86 14.18 13.04 False Morel (Fin) 0.8% 67.8% 12.0% N/A Mushroom Boletus.6% 32.11 1.6% 13.5 25.3% 2.1 2.9% 16.3% Oyster.0% 37.7 1.5% 0. raw (Jap) 0.6% 13.8% 10.Summary Table for RAW CULINARY SPECIALTY MUSHROOMS providing >10% RDI/AI of key vitamins /100g Nutrient Vit B6 (mg) Males 19-50 years Males over 50 years Females 19-50 years Females over 50 years Pantothenic acid (mg) Males 19 years and over Females 19 years and over RDI 1.9% 12.

08 1.3% Numeisugitake.05 1. raw (Jap) 0.32 22.5% 10.8% Yanagimatsutake.0% Shimeji Hatakeshimeji.3% 62.056 10.0% 11.5% 44.8% Maitake (USDA) 0.15 1.1 1.8% 26.3% Tamogitake.27 265 11.0% Nameko.48 41.081 1.5% 33. raw (Jap) 0.3 1.7 1.2% 19. raw (Jap) 0.8% Mushroom Enoki. raw (Jap) 0. raw (Can) 0.3 1.0% 33.8% 49.0% Kuroawabitake.8% 31. raw (Jap) 0.5% 65.0% 11.11 2.32 22.3% 35.044 1.25 20.12 1. raw (Jap) 0.Summary Table for RAW CULINARY SPECIALTY MUSHROOMS providing >10% RDI/AI of key vitamins /100g continued Nutrient Vit B6 (mg) Males 19-50 years Males over 50 years Females 19-50 years Females over 50 years Pantothenic acid (mg) Males 19 years and over Females 19 years and over RDI 1.056 0.3% Maitake. raw (USDA) 0.5 AI 6 4 Mushroom Oyster. raw (Jap) 0.09 1. raw (Jap) 0.79 13.77 29.44 0.067 17.5% 10.0% 10.07 0.27 Chanterelle. raw (Jap) 0. raw (Can) 0.12 1.294 21. raw (Can) 0.7% Winter Mushrooms (Jap) 0.075 17.91 31.136 Maitake.61 43.0% Matsutake.12 2.4% Enoki (USDA) 0.35 22.13 1.5% 10. raw (USDA) 0.5% 0.0% .6% 32.11 1.8% 47.0% 33.9% Morel.9% 26.97 32.4 23.3% Shimeji Honshimeji.

8 256.0% 13.0% 20.3% Nutrient Mushroom shiitake raw Lentinus edodes (USDA) Shimej Bunashimeji (Jap) 7 15.0% 44.7 14.2% 2 40.0% 120.3% 40.1mcg Boletus edible (Fin) 2.0% 20.3% 40.4 2 40.0% 55.0% 40.0% 13.3% 110.0% 44.0% Oyster Pleurotte (Fin) 1.0% 20.1% 11.0% Oyster (USDA) 0 0.3% Chantarelle (Fin) 5 11.2% Milk-cap Northern (Fin) 1.1% 11.0% 29.3% 88.7% 110.3% 256.5 2.0% 85.3% 88.0% 128.0% Oyster (Jap) 10 1 20.3% Shiitake dong gwoo (Fin) 2.0% 20.6% 15. Eringii.3% 40.4 88.3% False Morel (Fin) 5 11.3% Mushroom Boletus.2% 22. raw (Jap) 0 2 40.0% 85.0% 40.0% 10.1% 4.0% 10.3% 58.2% 22.0% 44.0% 266 .5 Oyster Pleurotus spp SFK-Ger 0.0% 19.3% Oyster.0% 36.7% 22. Russula (Fin) 5 11.0% 55.0% 29. Usuhiratake.0% 20.6 <0.0% 20.0% 13.0% 13.0% 36.0% 128.3 5.0% 60.0% 29.0% 29.1% 4.1 0.0% 29.0% 44.0% 29.1% 12.9 58.6 N/A 14.0% 13.6% Oyster.0% 60.1% 11.0% 20.4 88.1 Shiitake (Log grown) N/A N/A N/A 0.Summary Table for RAW CULINARY SPECIALTY MUSHROOMS providing >10% RDI/AI of key vitamins /100g Vit C (mg) Males 19 years and over Females 19 years and over Vit D (mcg) Males 19-50 years Males 51-70 years Males over 70 years Females 19-50 years Females 51-70 years Females over 70 years RDI 45 45 AI 5 10 15 5 10 15 Shiitake Nama-shiitake (Jap) 10 22. raw (Jap) 0 6 120.0% 13.0% 19.

raw (Can) 0 0.0% Numeisugitake.0% 295.5 590.7% .0% 51.0% 51.0% 40.1 562.0% 0 1 20.0% 281.7% 80.1 Winter Mushrooms (Jap) 1 1 Nameko.0% 10.0% 10.0% 30. raw (Jap) Kuroawabitake.0% 20.3% Morel.0% 10.0% 34. raw (Jap) 0 1 Shimeji Hatakeshimeji.0% 196.0% Nutrient Mushroom Oyster.0% 10.0% 10.0% Tr mg 1 20.0% 53.3% 106. raw (Jap) 2 4 80.0% 281.0% 40.0% 40.0% Tamogitake.0% 30. raw (Jap) Tr mg Tr mcg Maitake.0% 10.0% 35. raw (Jap) 0 18. raw (USDA) N/A 5.0% 34. raw (Jap) 20.0% 26.0% 187.0% 20.7% Maitake (USDA) 0 28.0% 10.3% Chanterelle.0% 20.0% 196.0% Tr mg 1 20.0% 20.0% 10.3% 562.1 102. raw (Can) 0 29.0% Maitake.1 Mushroom Enoki. raw (USDA) N/A 5. raw (Jap) Shimeji Honshimeji.0% 60.0% 26.0% 40.0% 80.0% 3 60.0% 53.0% 187. raw (Jap) 267 20.7% 20.3 106.0% 10.0% 20.0% Tr mg 4 80.0% 102.0% 295.Summary Table for RAW CULINARY SPECIALTY MUSHROOMS providing >10% RDI/AI of key vitamins /100g continued Vit C (mg) Males 19 years and over Females 19 years and over Vit D (mcg) Males 19-50 years Males 51-70 years Males over 70 years Females 19-50 years Females 51-70 years Females over 70 years RDI 45 45 AI 5 10 15 5 10 15 18.0% 10.0% 20.0% Matsutake. raw (Can) 0 0.7% 590.0% 10.0% 26.9 Enoki (USDA) 0 0.0% 26. raw (Jap) 1 1 20.0% 35.7% Yanagimatsutake.0% 20.0% 10.

8% 6mg male 19 and over 4mg female 19 and over Vitamin C M and F 15.1mg Female 19 years and over Riboflavin (B2) M 21. Raw (Jap) providing the greatest amount # >10% RDI provided by 6 of 33 mushrooms for M and F • Range male and females 19 and over 11.5% • Range female 19 and over – 10.2% 1.5% • Range female 19 and over 11 –65.7% 400mcg male and female 19 and over Vitamin B6 M 18.1mg Female 19-70: 1.2mg male 19 years and over 1.3mg male 19-70 : 1.7% F 19. Raw (Can) being the greatest contributor providing 29.1-22.1-85.2–43.3% • Range female 19 and over – 11. raw (Jap) # >10% RDI provided by 11 of 33 mushrooms for M and F • Range male and female 19 and over – 10-67.Table 3 Average %RDI/AI content for each Key Vitamin /100g Vitamin Average % Recommended Dietary Intake Thiamine (B1) M 17.5-25% Oyster.2% Shiitake Nama-shiitake (Jap) and Oyster (Jap) providing the greatest amount # >10% AI provided by 25 of 33 mushrooms for M and F • Range male and female 19 – 50: 14–590% • Range male and female 51-70: 10–295% • Range male and female 70 and over: 13.4% 1.1% 5mcg Male and female 19-50 10mcg male and female 51-70 15mcg male and female >70 Pantothenic acid Comments # >10% RDI provided by 19 of the 33 mushrooms for M and F • Range male 19 and over – 10 – 33.6% 45mg male and female 19 and over Vitamin D M and F 73.4-36. Usuhiratake.5mg female>50 M 26% F 37. raw (Jap) providing the greatest amount # >10% RDI provided by 13 of 33 mushrooms for M and F • Range male and female 19 and over – 10.45.7mg men>50 1.5% F 25.3mg female>70 Niacin M 39.3-197% Maitake.4% Shiitake (Log grown) and Oyster (Jap) providing the greatest amount # >10% RDI provided by M 30 and F 31 of 33 mushrooms • Range male 19 and over – 10 – 38.7% Shimeiji Hatakeshimeiji raw (Jap) providing the greatest amount # >10% AI provided by M 21 and F 22 of 33 mushrooms • Range male 19 and over 13.3% Yanagimatsutake.6mg men>70 1.6% 16mg male 19 and over 14mg female 19 and over Folate M and 16.7% Tamogitake.3mg male 19-50: 1.9.3mg Female 19-50: 1.1% F 44.5% Shimeiji Hatakeshimeiji raw (Jap) providing the greatest amount # >10% RDI provided by 31 of 33 mushrooms for M and F • Range male 19 and over – 14.5mcg per 100g 268 .1-75% • Range female 19 and over – 16.9% 1.4% F 18.

142 11.5% 110 11.15 12. raw (Jap) 0.1% Milk-cap Northern (Fin) N/A 55 N/A 290 10.12 380 10.1% Chantarelle (Fin) N/A 72 N/A 340 12.6% .15 12.0% 0. Eringii. raw (Jap) 0.5% 100 10.11 220 Oyster (Jap) 0.1% 16.0% 12.0% 0.0% 11.12 67 0.4% Oyster. Russula (Fin) N/A 72 N/A 340 12.1% 15.0% Oyster Pleurotte (Fin) N/A 110 Boletus edible (Fin) N/A 47 N/A 270 Mushroom Boletus.8% 0.06 112 11.Summary Table for RAW CULINARY SPECIALTY MUSHROOMS providing >10% RDI/AI of key minerals /100g Copper (mg) Males 19 years and over Females 19 years and over Phosphorus (mg) Males 19 years and over Females 19 years and over Manganese (mg) Males 19 years and over Females 19 years and over Potassium (mg) Males 19 years and over Females 19 years and over AI 1.1% 11.0% 269 10.2% 0.0% N/A 298 14.15 12.05 73 0.6% 12.4% Oyster Pleurotus spp SFK-Ger 0.0% 0.23 304 100 10.0% 11.7 1.13 N/A 10.0% 10. Usuhiratake.4% 10.244 20.3% 120 12.0% 10.0% 12.5% 120 12.0% 10.9% 12.07 460 Oyster.2% 11.16 340 Oyster (USDA) 0.0% 13.0% 0.5 5 AI 3800 2800 Nutrient Shiitake Nama-shiitake (Jap) 0.23 280 Shiitake dong gwoo (Fin) N/A 73 N/A 224 Shiitake (Log grown) N/A 39 N/A N/A Mushroom shiitake raw Lentinus edodes (USDA) Shimej Bunashimeji (Jap) 0.0% 0.1% False Morel (Fin) N/A 72 N/A 340 12.113 420 11.2 RDI 1000 1000 AI 5.

06 230 Maitake.7% 204 . raw (Jap) 0. raw (Jap) 0.0% 0.2% 30.587 0.27 15.7% Shimeji Hatakeshimeji.0% 74 0.0% Enoki (USDA) 0.15 12.05 260 Tamogitake.05 330 11.1% 20.19 11. raw (Jap) 0.7% 10.252 14.2% 15.2 RDI 1000 1000 AI 5.12 410 Maitake (USDA) 0.5% 10.7% 70 0.7% 11.1% 411 10.0% 74 19.5% 0.8% 29.353 20.8% 14.113 420 11.244 14.9% 10.1% 194 Maitake.1 300 0. raw (Jap) Shimeji Honshimeji.14 11.4% 0. raw (Jap) 0.4% 19.0% 13.5% 100 0.8% 21. raw (Jap) Kuroawabitake.8% 26. raw (USDA) 0.1 110 11.107 105 10.17 280 10.5 5 AI 3800 2800 Mushroom Oyster.625 36.4% 20.0% 11.7% 110 0.075 359 12.5% 130 13.4% 57 0.32 18.07 340 12.6% 506 13.252 14.8% 52.0% 75 0.06 190 0.2 11.0% 0.8% 11. raw (Jap) Numeisugitake.36 21.079 368 13.0% 0.7 1.8% 21.059 270 10.3% 18. raw (Jap) 10.11 66 0.8% 16. raw (Can) 0.08 360 12.0% 10.091 109 10.9% 22.0% 11.059 204 Chanterelle.24 14.9% 10.7% 85 0.9% 0. raw (Can) 0. raw (Can) 0.8% 14.Summary Table for RAW CULINARY SPECIALTY MUSHROOMS providing >10% RDI/AI of key minerals /100g continued Copper (mg) Males 19 years and over Females 19 years and over Phosphorus (mg) Males 19 years and over Females 19 years and over Manganese (mg) Males 19 years and over Females 19 years and over Potassium (mg) Males 19 years and over Females 19 years and over AI 1.0% 0.286 Morel.1% Winter Mushrooms (Jap) 0.8% 65 0.1% 15.0% 40 0.1% Nameko.0% 12. raw (Jap) 0.8% Mushroom Enoki.3% 120 12. raw (USDA) 0.0% Matsutake.07 300 10.7% Nutrient Yanagimatsutake.0% 0.

7 0.7 0.33 Oyster Pleurotte (Fin) 1.3 Oyster.6% 0.7 Oyster (USDA) 2. Russula (Fin) 14.4 Shiitake dong gwoo (Fin) 0.5% 0.6 Oyster (Jap) N/A 1 12.7 2.03 Shimej Bunashimeji (Jap) N/A 0.7 12.9% 0.9 11.9 Mushroom Boletus.73 1.0% 0.0% 10.1 20.5% 12.4% 15.5% 0.4% 11. raw (Jap) N/A 0.1% 23.2 0.0% 33.5 0.8% 1.0% 2.7% 65.4 Oyster.7 1.6 0.8% 2.3 10.7 33.Summary Table for RAW CULINARY SPECIALTY MUSHROOMS providing >10% RDI/AI of key minerals /100g Selenium (mcg) Males 19 years and over Females 19 years and over Zinc (mg) Males 19 years and over Females 19 years and over Iron (mg) Males 19 years and over Females 19-50 years Females over 50 years RDI 70 60 RDI 14 8 RDI 8 18 8 Nutrient Shiitake Nama-shiitake (Jap) N/A 0. Eringii.8% 15.0% 0.4 Boletus edible (Fin) 11 15.0% Milk-cap Northern (Fin) Oyster Pleurotus spp SFKGer 0.7 33.6 1 12. Usuhiratake.2 0.3 0. raw (Jap) N/A 0.0% 33.41 16.8 Shiitake (Log grown) N/A N/A Mushroom shiitake raw Lentinus edodes (USDA) 5.23 15.3% 0.8 10.6 Chantarelle (Fin) 18 25.7 33.0% 271 .7% 18.8% 15.6% 16.8 False Morel (Fin) 39 55.3% 10.3% 0.8% 15.8% 0.0% 33.5% N/A 0.3 0.77 1.7% 30.

2 0.47 43. raw (Jap) N/A 0. raw (Jap) 10.3% 43.03 12.6 0.2 0.3 Chanterelle.1 1.0% 10.2 0.2 0.0% 10.3 0.8 10.77 1.18 152. raw (Jap) N/A 0.4% 19. raw (Jap) N/A 0. raw (Jap) N/A 0.Summary Table for RAW CULINARY SPECIALTY MUSHROOMS providing >10% RDI/AI of key minerals /100g continued Selenium (mcg) Males 19 years and over Females 19 years and over Zinc (mg) Males 19 years and over Females 19 years and over Iron (mg) Males 19 years and over Females 19-50 years Females over 50 years RDI 70 60 RDI 14 8 RDI 8 18 8 Nutrient Mushroom Oyster.4% 1.4 0. raw (Jap) N/A 0.2 2.65 1.8% 13.6% Winter Mushrooms (Jap) N/A 0. raw (Jap) N/A 0.6 Kuroawabitake.7 0. raw (USDA) 2. raw (Can) 2.4% Mushroom Enoki.8 13.3% Maitake.15 14.8% Numeisugitake.75 0.5 0.33 16.5% 25.61 1.5 10.5 0.3% 16.6% Enoki (USDA) 2.0% 14.3% 67.7 Maitake.75 Yanagimatsutake.8% Nameko.0% Shimeji Hatakeshimeji.71 3.8 16.6% 16.3% Maitake (USDA) 2. raw (USDA) 2.4 0. raw (Can) 2.6 1.6 Tamogitake.3 272 . raw (Jap) Shimeji Honshimeji.4% 14.6% 13.09 13.0% 0.7% 152.4% Morel.6 N/A 0.6 0.5 Matsutake. raw (Can) 2.8 N/A 0. raw (Jap) N/A 0.8% 13.1 13.2 0.

2% 70mcg male 19 and over 60mcg female 19 and over Zinc M 14.7% 3800mg male 19 and over 2800mg female 19 and over Selenium M 29.7% Only 5.4% Morel .7% female Morel.1% Morel.3-65% False Morel (Fin) providing the greatest amount # >10% RDI provided by M 1 and F 10 of 33 mushrooms • Males 19 and over only one at 14.5% • Range females 19 and over 10-25.3% F 34.3% Morel.4% F 20% 1.7-55.5mg male 19 and over 5mg female 19 and over Potassium M 11.7% 1000mg male and female 19 and over Manganese M 10.Raw (USDA) provided >10% at 14. # >10% RDI provided by M F 16 of 33 mushrooms • Male 19 and over and females over 50 Range 10152.4% Morel. Raw (USDA) providing the greatest at 12.2mg Female 19 and over Phosphorous M and F 11.3% F 12.7% and 11. #>10% RDI provided by 4 of 33 mushrooms for M and F • Range male 19 and over – 15.5% F 12.1% F 27.2-36.8% • Range female 19 and over – 10-52.7% 8mg male 19 and over 18mg females 19-50: 8mg female over 50 Comments # >10% RDI provided by M 12 and F 19 of 33 mushrooms • Range male 19 and over – 11. raw (USDA) providing the greatest amount # >10% RDI provided by 15 of 33 mushrooms for M and F • Range male and female 19 and over – 10-19.1% Chanterelle.7 % Only F 11.7% • Range female 19 years and over – 18. Raw (USDA) Providing the greatest amount # >10% RDI provided by M 7 and F 23 of 33 mushrooms • Range male 19 and over – 10-13.3% • Range female 19 years and over – 10-18.5%. Raw (USDA) providing the greatest amount.3% 14mg males 19 years and over 8mg Females 19 years and over Iron M 28.Table 4 Average %RDI/AI content for each key mineral /100g Mineral Average % Recommended Dietary Intake Copper M 17. Raw (USDA) Providing the greatest amount # >10% AI provided by 1 of 33 mushrooms for M and F • Male 19 and over – 10.7mg male 19 and over 1.2mg/100g 273 .

09 0.2% 26.34 26.6% 11.2% 21.1% 35.3 RDI 16 14 RDI 400 400 1.6% 28.1% N/A .0% 21.2% 20.7 16.593 10.9% 25.1 1.5% 25.9% 18 Mushrooms.8% 7.1% 36.4% 11 Common Mushroom Boiled (Jap) 0.402 30.9% 26.1% 50.096 0.073 0.6% 3.28 21.4% 29.1% 23 Mushrooms canned (Ger) 0.19 14.3% 60. golden.1% 18.2% 2.9% 39.03 0.02 0.9% 42.3% 23.8% 41.1% 18.2% 26.081 0.021 0.9% 4.4% 16.085 0.5% 21. canned Agaricus bisphorus (Den) 0.3% 23.9% 31.4% 38.46 27.2% 16 0.4% 38. canned in brine. fried in corn oil (UK) 0.4% 12 0.9% 19.5% 20 Mushrooms. Asian.2% 33.2% 5.987 24.9% 0. white.1% 4.22 0. drained solids (USDA) Thiamin (B1) (mg) Males 19 years and over Females 19 years and over Riboflavin (B2) (mg) Males 19-70 years Males over 70 years Females 19-70 years Females over 70 years Niacin equivalents (B3) (mg) Males 19 years and over Females 19 years and over Folate (mcg) Males 19 years and over Females 19 years and over RDI 1. canned in brine solids (Jap) 0.2% 16 0.9% 17.3% 30. stirfried (no oil) Agariscus bisphorus (Aust) Mushroom.9% 26.6% 1. boiled.073 0.3 23. stir fried (USDA) Mushroom.3% 23.5% 30.431 33.06 0. canned.3 1.9% 31.Summary Tables for COOKED COMMON MUSHROOMS (Agaricus bisporus) providing >10% RDI/AI of key vitamins /100g Nutrient Mushrooms.1% 18.5% 15.3% 19 Common mushroom.3 14. without salt (USDA) 0. drained (Aust) 0.3% 14.2% 33.3 14.8% 27.8% 18.4% 16.8% 27.0% 11. common.3% 30. with salt (USDA) 0.34 26. drained.8% 27.46 27.2% 5.35 33. canned in brine solids (Jap) 0.3% 1 Mushroom.6 1.02 Mushrooms.2 1.5% 17.1% 2 12.07 25. common.23 19. common Fried in Butter (UK) 0.9% 28.1% 4.042 0.661 50. white microwaved (USDA) Mushrooms.9% 39. cooked.35 33.04 0.05 0.2% 21.1 RDI 1. drained.9% 50.5% 2.1% 27 11.55 274 2 N/A 43.463 35. cooked.3 23.2% 2.431 33. white microwaved (Can) Mushrooms.24 18.4% 11 Mushrooms.9% 18 Mushrooms.5% 14.3 23. boiled.5% 1 Matsutake.09 0.06 0.05 1.

073 0.2% 23.926 35.0% 6.7% 18 Mushroom.8% 1. drained (Aust) 10.2% 5. drained (Can) 0. white.1 31. straw.7% 7.6% 22.2% 36.9% N/A 0.8% 27.8% 35.0% 6.8% 34.7% 19.021 Mushroom Portabella grilled Agaricus bisporus (USDA) 0.5% Champignon.4% 18.6% 44.0% 25.8% 41.1% 13.7% 19 36.12 0.49 37.02 0.1% 6.1% 12 Mushroom in vinegar (Fin) 0.37 Champignon.6% 29. drained solids (Can) 0.1% 44.403 31.1% 43.255 39.4% 34.0% 10.8% 12. straw. drained solids (USDA) 0.1% 44.3% 23.8 13.9% 36.3 23.9 Mushroom.2% 15.2% Mushroom Portabella exposed to UV light grilled A bisporus (USDA) 0. drained solids (Can) 0.3 RDI 16 14 RDI 400 400 0 0.4% 34.5% 13. grilled (Can) 0.7% 19 0.3 Mushroom fried Agaricus bisporus (Fin) 0.38 29.86 30.1 RDI 1.3 64.403 31.072 0.8% 32.08 0.3% 23.1% 44.1% 4.943 12.1% 26.604 28. fried Agaricus bisphorus (Fin) 0.3 1.9% 39.0% 51.6% 53.2 1.6% 28.7% 30.1% 18.4% 28.4% 10.224 275 20 38 .255 39. canned Agarisuc bisphorus (Fin) 0. boiled (Fin) 0.9% 42.2 45. drained with salt (Can) 0. canned.096 0.25 19.0% 6.5% 29.2% 5.085 0.07 Nutrient Mushroom. canned.6% 31.072 0. boiled.7% 10.3 23.03 0.1% 33. canned in brine.2% Mushroom.6% Mushroom Portabella (Portabello).1 1.073 0.4% 18 Boletus edible.9% 12 31.403 31.43 33.1 38.0% 25.013 0. boiled.072 0.07 Mushroom.9% 20 1.9 36.1 0.255 39.86 30.14 10.1% 4. Asian.6% 4.46 35. straw.5% 37.6 1.9% 42.463 Mushroom Canned.0% 25.013 0.7% 18 Mushroom.1% 18.7% 19 36.6% 31.1% 35.4% 73.8% 27. stir-fried (Can) 0.Summary Tables for COOKED COMMON MUSHROOMS (Agaricus bisporus) providing >10% RDI/AI of key vitamins /100g continued Thiamin (B1) (mg) Males 19 years and over Females 19 years and over Riboflavin (B2) (mg) Males 19-70 years Males over 70 years Females 19-70 years Females over 70 years Niacin equivalents (B3) (mg) Males 19 years and over Females 19 years and over Folate (mcg) Males 19 years and over Females 19 years and over RDI 1.

canned Agaricus bisphorus (Den) 0. Asian.Summary Tables for COOKED COMMON MUSHROOMS (Agaricus bisporus) providing >10% RDI/AI of key vitamins /100g Vit B6 (mg) Males 19-50 years Males over 50 years Females 19-50 years Females over 50 years Pantothenic acid (mg) Males 19 years and over Females 19 years and over Biotin (mcg) Males 19 years and over Females 19 years and over RDI 1.16 36. boiled.3 1. with salt (USDA) 0.0% 54. cooked.061 0.01 0.7% 49.19 1.05 N/A Mushroom.2% 14. cooked.43 23.8% 35.2% 54.811 13.5% 20.0% Mushrooms. white microwaved (USDA) Mushrooms.0% Mushrooms canned (Ger) 0. white microwaved (Can) Mushrooms.06 0. drained.3% 20.7% 32.06 1 16.7 55.7% 32.6% 11. drained solids (USDA) Mushrooms.45 24.16 36.0% Common Mushroom Boiled (Jap) 0.8 13.8% Mushroom.0% 8 26. boiled. golden. drained (Aust) N/A N/A Nutrient Mushrooms. without salt (USDA) 0.96 32.01 0.0% 54.96 32.3 1.0% N/A Mushrooms. white.3% 16. common.3% N/A 0.7% 66.095 2.0% N/A Mushrooms.6% 12.3% 35. common.3% 64.11 N/A Matsutake.8% N/A Common mushroom. fried in corn oil (UK) 0 1. canned in brine solids (Jap) 0.0% 8 26. canned in brine. common Fried in Butter (UK) 0. stir-fried (no oil) Agariscus bisphorus (Aust) 0. stir fried (USDA) 14.0% N/A 0.04 2.049 1.042 1.095 2. canned.4 23.0% N/A 0.7% 49.3% 35.7% 25.7% 276 N/A .4 23.2% 36.3% N/A Mushrooms.7 1.08 1.17 36.5 AI 6 4 AI 30 25 0. drained.049 1.0% 16 53.0% N/A Mushroom. canned in brine solids (Jap) 0.

grilled (Can) 0.5% 12.3% N/A 16. white.2% 21.412 10.262 21.45 24.07 N/A N/A Mushroom in vinegar (Fin) 0.014 0.07 N/A N/A Mushroom.0% 20.014 0.Summary Tables for COOKED COMMON MUSHROOMS (Agaricus bisporus) providing >10% RDI/AI of key vitamins/100g continued Vit B6 (mg) Males 19-50 years Males over 50 years Females 19-50 years Females over 50 years Pantothenic acid (mg) Males 19 years and over Females 19 years and over Biotin (mcg) Males 19 years and over Females 19 years and over RDI 1. canned in brine. straw.7% 277 .095 2.0% 31. straw. drained with salt (Can) 0. boiled (Fin) 0.16 36.0% N/A Mushroom.0% 54. boiled.262 21.5% 16.2% 36.3 1. canned. fried Agaricus bisphorus (Fin) 0. drained (Can) 0. stir-fried (Can) 0.3% N/A Mushroom Canned.2% 21. canned.0% 31.4% 16.16 36.05 Boletus edible.6% N/A Mushroom. drained solids (Can) 0.262 21.21 Mushroom fried Agaricus bisporus (Fin) 0.061 0.6% N/A Mushroom Portabella exposed to UV light grilled A bisporus (USDA) 0.5 AI 6 4 AI 30 25 Nutrient Mushroom.3 1.3% N/A Mushroom Portabella grilled Agaricus bisporus (USDA) 0. canned Agarisuc bisphorus (Fin) N/A N/A N/A N/A N/A N/A N/A N/A 0. drained solids (Can) 0.5% 14.122 1.7 1.811 21.0% 54.412 10. straw.0% N/A Mushroom.122 1. Asian. boiled.0% 18.042 1. drained (Aust) N/A Champignon.0% 31.3% N/A Mushroom.6% N/A Mushroom Portabella (Portabello).28 Champignon. drained solids (USDA) 0.122 1.095 2.

2 Mushrooms. white microwaved (USDA) Mushrooms.3 0 0 0. drained. golden. common.Summary Tables for COOKED COMMON MUSHROOMS (Agaricus bisporus) providing >10% RDI/AI of key vitamins/100g Vit C (mg) Males 19 years and over Females 19 years and over Vit A (Retinol Equivalents) (mcg) Males 19 years and over Females 19 years and over Vit D (mcg) Males 19-50 years Males 51-70 years Males over 70 years Females 19-50 years Females 51-70 years Females over 70 years RDI 45 45 RDI 900 700 AI 5 10 15 5 10 15 20.0% 13. stir fried (USDA) Matsutake.1 10 0 Mushrooms canned (Ger) 1. canned Agaricus bisphorus (Den) 2. drained (Aust) 3 59 N/A Mushrooms. fried in corn oil (UK) 1 tr 0 Common Mushroom Boiled (Jap) 0 0 1 20.0% Common mushroom.3 0 0 0. canned in brine solids (Jap) 12. canned in brine solids (Jap) 0 0 2 40.0% 120. cooked.0% 10. boiled. with salt (USDA) 4 0 0.2 Mushrooms.1 . without salt (USDA) 4 0 0.0% Mushroom. drained.0% 13.0% 20. common Fried in Butter (UK) 1 85 Mushrooms.3% 40. boiled.3% Tr mg 0 6 120.0% 60.0% 40. white microwaved (Can) Mushrooms. common.7 N/A N/A Mushroom.0% 20. canned.1% 278 0. cooked. canned in brine.2 0 0 0. drained solids (USDA) 0 0 0.0% 60.0% 40. stir-fried (no oil) Agariscus bisphorus (Aust) 2 23 N/A Mushroom. white. Asian.2 Mushrooms.0% 10.0% Nutrient Mushrooms.

0% 141.0% Mushroom fried Agaricus bisporus (Fin) 6.1 N/A 15.5 10.0% .0% 10.0% 30.9 N/A 0.0% 90.5 90.3 Mushroom Portabella (Portabello).0% 158. drained with salt (Can) 4 0 0.0% Mushroom. drained solids (Can) 1.5 0 0.3 Mushroom Portabella exposed to UV light grilled A bisporus (USDA) 0 N/A 14. drained (Can) 4 0 0.9 N/A 4. drained solids (Can) 0 0 N/A Mushroom.0% 32. fried Agaricus bisphorus (Fin) 0.0% 1 N/A 0.2 Mushroom Portabella grilled Agaricus bisporus (USDA) 0 0 0.6% 279 282.0% 10. boiled. boiled (Fin) 2.3% 316.Summary Tables for COOKED COMMON MUSHROOMS (Agaricus bisporus) providing >10% RDI/AI of key vitamins /100g continued Vit C (mg) Males 19 years and over Females 19 years and over Vit A (Retinol Equivalents) (mcg) Males 19 years and over Females 19 years and over Vit D (mcg) Males 19-50 years Males 51-70 years Males over 70 years Females 19-50 years Females 51-70 years Females over 70 years RDI 45 45 RDI 900 700 AI 5 10 15 5 10 15 Nutrient Mushroom.0% 105. drained (Aust) 2 53 N/A Champignon. straw.8 96.0% 48. straw.0% Mushroom.5 N/A 4. canned in brine. stir-fried (Can) 0 0 0. Asian.0% 282.0% 45.6% 13.0% Mushroom.0% 94.8 316. canned.0% 158.2 Mushroom Canned. boiled.5 10. drained solids (USDA) 0 0 N/A Champignon.0% 48. canned Agarisuc bisphorus (Fin) 13. grilled (Can) 0 0 0.0% 105.0% 94.3% Boletus edible.0% 30. white. canned.0% 32.0% 96.2 Mushroom.1 141. straw.2 Mushroom in vinegar (Fin) 1.0% 45.

6 % only F 12. Asian.Table 5 Average %RDI/AI content for each key vitamin /100g Vitamin Thiamine (B1) Average % Recommended Dietary Intake Comments M 14.6mg men>70 1. common. boiled (Fin) providing thte greatest amount # >10% RDI provided by 1 of 30 mushrooms for M and F Boletus edible.common Fried in butter (UK) # >10% RDI provided by 9 of 30 mushrooms for M and F • Range male and female 19 –50: 10–316% • Range male and female 51-70: 10–158% • Range male and female 70 and over: 17-105.5% • Range female 19 and over 12. boiled (fin) providing the greatest amount # >10% AI provided by M 19 and F 21 of the 30 mushrooms • Range male 19 and over 13.8% Mushroom. boiled (Fin) providing thte greatest amount 1.6% F 15.3mg male 19-70: 1.7% 30mg male 19 and over 25mg female 19 and over Vitamin C 45mg male and female 19 and over # >10% RDI provided by 1 of 30 mushrooms Mushroom. canned in brine. stir-fried (no OIL) agaricus bisporus (Aust) providing the greatest amount # >10% RDI provided by M 24 and F 25 of 30 mushrooms • Range male 19 and over 10–64.9% F 35.6% 6mg male 19 and over 4mg female 19 and over Biotin M 40. common.7% F 30. fried Agaricus Bisporus (Fin) being the greatest contributor providing 15.3mg females19-50.7mg males 50 and over 1.6% F 48.1mg Female 19-70:1.2mg male 19 years and over 1.7-60.1% Mushroom. Golden.1mg Female 19 years and over Niacin (B3) M 30% F 33.5mg females 50 and over Pantothenic acid M 25. stir-fried (no OIL) agaricus bisporus (Aust) providing the greatest amount .8% • Range female 19 and over 12.3mg males 19-50: 1. common. stir-fried (no OIL) agaricus bisporus (Aust) providing the greatest amount # >10% AI provided by 4 of the 30 mushrooms for M and F • Range male 19 and over 26.4% F 16.3% Maitake.7% • Range female 19 and over 32 –66.4% • Range female 19 and over 11.6% Boletus edible. 1.5% 400mcg male and female 19 and over Vitamin B6 M 15. drained (Aust) providing the greatest amount # >10% RDI provided by 25 of 30 mushrooms for M and F • Range male 19 and over 10.3–36. Fried Agaricus Bisporus (Fin) Vitamin A M and F 13.7–55.8mcg per 100g Riboflavin (B2) # >10% RDI provided by 2 of the 30 mushrooms for M and F Mushroom.3% 1.3mg female>70 280 # >10% RDI provided by 3 of 30 mushrooms for M and F • Range male 19 and over 11.2% • Range female 19 and over 10.7 -21.9% M 25.8–50.9% 900mcg male 19 and over 700mcg female 19 and over 5mcg Male and female 19-50: 10mcg male and female 51-70: 15mcg male and female >70 # >10% RDI provided by 1 of 30 mushrooms Mushroom.4% 16mg male 19 and over 14mg female 19 and over Folate M & F 13.1% only Vitamin D M and F 80.3 –54.5% 1.3% Mushroom.5% Boletus edible.1 –73.2 – 21.

canned.2% 25. cooked.3% 15 300 281 69. boiled.2% 65.6% 340 12.0% 0.6 12.1% 22.2 RDI 1000 1000 AI 460 460 AI 3800 2800 RDI 70 60 0. drained solids (USDA) Mushrooms.48 28.8% 36 130 28.2% 30.1% N/A 0.291 17.7% 17 488 12.7% 51.1% 12 17.4 23.3% 28.7 1.6% 42. drained. common.3% Mushrooms.1% 20.2% 40. stirfried (no oil) Agariscus bisphorus (Aust) Mushroom.0% 19.4 23.0% 150 32.4% 18 25.9% N/A .7% 356 12.8% 49 69.5% 33.8% 127 12.37 21.19 11.5% 33.6% 66 425 92.6% 32.1 15.2% 40.7% 13.Summary Tables for COOKED COMMON MUSHROOMS (Agaricus bisporus) providing >10% RDI/AI of key minerals /100g Copper (mg) Males 19 years and over Females 19 years and over Phosphorus (mg) Males 19 years and over Females 19 years and over Sodium (mg) Males 19 years and over Females 19 years and over Potassium (mg) Males 19 years and over Females 19 years and over Selenium (mcg) Males 19 years and over Females 19 years and over AI 1.3% 0.8% 17.6% 48.8% 30.3 Mushrooms canned (Ger) 0.5% 12 396 10.6% 42.0% 76 5 190 3.5% Nutrient Mushrooms.31 18.645 37.1 41.7% 30.3% 110 11. canned in brine solids (Jap) Mushroom.0% 11. canned Agaricus bisphorus (Den) 0.0% 10.504 29.3% 2 N/A Mushroom.7% 11.235 13. boiled.8% 127 12.9% 53.0% Mushrooms.9 17. canned in brine solids (Jap) 0.2% 15.2% 0.5% 10.0% 0.37 21.36 21.4% 18 25. canned in brine. white. drained. common Fried in Butter (UK) 0. stir fried (USDA) Mushrooms.9% 23.3% 585 65. white microwaved (USDA) Mushrooms.4% 14. white microwaved (Can) Mushrooms. with salt (USDA) Common Mushroom Boiled (Jap) Common mushroom. fried in corn oil (UK) 0.8% 19.4% 92.2% 24 4.0% 99 6 310 11.8% 17. Asian.48 28.8% 0.1% 85 N/A Matsutake.0% 4 340 12.8% 20.1% 20.7% 30.0% 87 238 51.1% 12 17.4 19.0% 69 319 121 8. drained (Aust) 0.8% 55 350 76. common.1% 13.8% 30.9 19.3% 100 10.7% 12.7% 17 488 12.1% 24.06 20.1% 76.504 29. cooked.3% 105 10.0% 0.7% 12. golden.4% 129 0.8% 208 29. without salt (USDA) Mushrooms.3% 14.4% 20.0% 87 2 356 12.

boiled (Fin) N/A 72.8% 19.5% 11 437 11.5% 15.7% 415.2 RDI 1000 1000 AI 460 460 AI 3800 2800 RDI 70 60 240 52. grilled (Can) 0.9 10.2 21.9% 12 425 384 282 55.5% 78 Mushroom.133 11.5% 15.5% 13.3% 105 Mushroom Canned.9 19.5% Mushroom Portabella exposed to UV light grilled A bisporus (USDA) 0.0% 190 Mushroom in vinegar (Fin) N/A 68.Summary Tables for COOKED COMMON MUSHROOMS (Agaricus bisporus) providing >10% RDI/AI of key minerals /100g continued Copper (mg) Males 19 years and over Females 19 years and over Phosphorus (mg) Males 19 years and over Females 19 years and over Sodium (mg) Males 19 years and over Females 19 years and over Potassium (mg) Males 19 years and over Females 19 years and over Selenium (mcg) Males 19 years and over Females 19 years and over AI 1.1% 61 11.504 29.6% 21.9% 32.2% 25 Nutrient Mushroom.1 Mushroom fried Agaricus bisporus (Fin) N/A 90 257.5% 27.6% Mushroom Portabella (Portabello).4 10. stir-fried (Can) 0.7% 25.1 18.5% Mushroom.5% 83. boiled.5% 11 437 11.6% 42.0% 14.3% 36.04 48 Champignon.9% 436.1% 22.9 24.4% 36.6% 13.9 31.5% Mushroom.5% 13.0% 87 2 356 Mushroom.235 13.389 22.7% 11.9% 10.3% 54.9% 22 31.9 17.7% 213.4% 83.8% 12.1% 61 384 83.4% 135 13.1% 24.9% 14. drained solids (Can) 0.389 22. canned.3% 15.2 Champignon.5% 13.389 22.504 29.3% 36.5% N/A 2.9% 23.2% 21.0% 87 238 51.5% 11.2% 32.6% 66 Mushroom Portabella grilled Agaricus bisporus (USDA) 0.7% 25.9 31. drained (Aust) 0.1% 129 78 4.9% 10. Asian. drained solids (USDA) 0.3% 396 92.3 11.2 21. straw.4 46. fried Agaricus bisphorus (Fin) N/A 119. drained with salt (Can) 0. canned Agarisuc bisphorus (Fin) N/A 76 520 113.291 17.7% 323 11.4 983 213.133 11.6% 21. boiled.9% 32.7% 21. straw.0% 19.5% 92.4% 135 13.2 Boletus edible. canned. canned in brine.6% 42.3 11.9 31.1 . drained (Can) 0.7 1.4% 135 13.1% 28. drained solids (Can) 0.4% 14.0% 113.5% 11 437 11.3 9.8% 16.0% 12.5% 15.2 55.8% 417.4% 83.4 19. straw.5% 15.7% 13.2% 52.5% 15.7% 356 Mushroom.3% 36.9% 32.3% 13.7% 51. white.

white microwaved (Can) Common mushroom.8 10.74 21.5% 11. drained.93 Mushrooms canned (Ger) N/A Mushroom. cooked.6 0. common. drained (Aust) 0. stir-fried (no oil) Agariscus bisphorus (Aust) 1. Asian.84 10.5% 283 12.87 10.5 1 12.6% 13.06 Mushroom.5% 10.8% N/A Mushrooms.5% 12.7 Mushroom. white. boiled. with salt (USDA) 0.3% N/A 0. boiled. drained. golden.0% 10.73 0. common. canned in brine solids (Jap) 1 Matsutake.72 0.5% 11 Mushrooms.0% 10. common Fried in Butter (UK) 0.74 21.87 10.5 1 12. canned Agaricus bisphorus (Den) 0. canned in brine.8% N/A Mushrooms. canned in brine solids (Jap) 0.3% 0.5% 0 .5% 12. canned.33 N/A 0. cooked.9% 1. white microwaved (USDA) Mushrooms.57 0.8% 21.0% N/A 3.5 1 0 12. drained solids (USDA) 0.25 N/A Mushrooms.3% 41.3% N/A 0.5% 4 Common Mushroom Boiled (Jap) 0.73 0. stir fried (USDA) 0.8% 21.33 N/A Mushrooms. without salt (USDA) 0.8 10.3 41.Summary Tables for COOKED COMMON MUSHROOMS (Agaricus bisporus) providing >10% RDI/AI of key minerals /100g Zinc (mg) Males 19 years and over Females 19 years and over Iron (mg) Males 19 years and over Females 19-50 years Females over 50 years Iodine (mcg) Males 19 years and over Females 19 years and over RDI 14 8 RDI 8 18 8 RDI 150 150 Nutrient Mushrooms.9% 1.79 N/A 0.5% 0.0% N/A 18.4 12.3 Mushrooms. fried in corn oil (UK) 0.5 0.

5% 0 15. canned. drained with salt (Can) 0. canned Agarisuc bisphorus (Fin) 0.3 41.87 10.0% 15.3% 14.5% 1. drained (Aust) 0.8 15.4 N/A Mushroom Portabella exposed to UV light grilled A bisporus (USDA) 0. boiled.9% 284 18.4 N/A Mushroom.8% 21.8 10.9% N/A Mushroom. fried Agaricus bisphorus (Fin) 0.79 N/A Mushroom Portabella grilled Agaricus bisporus (USDA) 0.9% 1.3 1 Champignon. drained solids (USDA) 0.5 0.8% 21.65 0.57 0.5 Mushroom in vinegar (Fin) 0. Asian.74 21.2 17.5% 32. canned in brine.3% 15.67 1.67 1.4 Champignon.3% Nutrient Mushroom.0% 23 11.72 0.4% 17.43 10. white.43 17.8% N/A Mushroom.0% 1.65 0.3% 17.3% 14. straw.3 41.Summary Tables for COOKED COMMON MUSHROOMS (Agaricus bisporus) providing >10% RDI/AI of key minerals /100g continued Zinc (mg) Males 19 years and over Females 19 years and over Iron (mg) Males 19 years and over Females 19-50 years Females over 50 years Iodine (mcg) Males 19 years and over Females 19 years and over RDI 14 8 RDI 8 18 8 RDI 150 150 12. drained solids (Can) 0. canned.87 10.6 0. boiled. drained solids (Can) 0.9% 17.3% 2. stir-fried (Can) 0.9 Mushroom.5% 12. straw.74 21.9 Boletus edible.5 Mushroom fried Agaricus bisporus (Fin) 0.65 0.0% 10. grilled (Can) 0.3% 3.8% N/A Mushroom.6 32.0% 11.5% 0 0.9% N/A .9% 1. drained (Can) 1.25 N/A Mushroom Canned.4 N/A Mushroom Portabella (Portabello). straw. boiled (Fin) 1.

3% • Range female 19 and over – 14.3% 70mcg male 19 and over 60mcg female 19 and over Zinc M 10% only F 12.3-46.4-18. 14. stir fried (NO oil) agaricus bisporus (Aust).8% F 14.4% 460 mg male and female 19 and over Potassium M 11.8% 1000mg male and female 19 and over Sodium M and F 77.1% 14mg males 19 years and over 8mg Females 19 years and over Iron M 19.7% Mushroom in Vinegar (Fin) Provide the greatest amount # >10% AI provided by M 11 and F19 of 30 mushrooms • Range male 19 and over – 10.8% Mushroom Common.2mg Female 19 and over Phosphorous M and F 12.8% 8mg male 19 and over 18mg females 19-50 years 8mg females 51 and over Iodine M and F 15.Females only Boletus edible.1-53.Table 6 Average %RDI/AI content for each key mineral /100g Mineral Average % Recommended Dietary Intake Copper M 23.3% Mushroom Fried agaricus bisporus (Fin) and Matsutake.3-213.9% Mushroom Common. boiled (Fin) providing the greatest amount # >10%RDI provided by 18 of 30 mushrooms for M and F • Range male 19 and over.4-15. 10 – 41.3% F 28. canned agaricus bisporus (Fin) 285 .37.4% 3800mg male 19 and over 2800mg female 19 and over Selenium M 24.9-17.3% • Range female 19 -50. stir fried (NO oil) agaricus bisporus (Aust).9% • Range female 19 and over – 11.8% Mushroom Common. Provide the greatest amount # >10%RDI provided by 21 of 30 mushrooms for M and F • Range male 19 and over – 12.4% • Range female 19 years and over – 11.5% . Provide the greatest amount # >10% AI provided by 15 of 30 mushrooms Range male and female 19 and over – 28.1% F 18.2.8% 1. stir fried (NO oil) agaricus bisporus (Aust).3% • Range over 50 years and over – 10 – 41. F23 of 30 mushrooms • Range male 19 and over – 11.7mg male 19 and over 1. canned in brine solids (Jap) Provided the greatest amounts Only 1 mushroom from 30 provided >10 RDI this being champignion.1-20.1% F 30.3% only 150mcg male and female 19 and over Comments # >10% AI provided by M 21. Provide the greatest amount # >10% RDI provided by 11 of 30 mushrooms • Range male and female 19 and over – 10-20.3-54% Mushroom in Vinegar (Fin) Provide the greatest amount # >10%RDI provided by M 1 and F 10 of 30 mushrooms • Range 10.

3 54. boiled (Jap) 3.5 % of the AI26 for fibre for both male and females aged 19 years and over whereas the common variety mushroom provides an average of 8.8% Nameko canned in brine (Jap) 2.7 15.8% Winter mushroom bottled in seasoning (Jap) 4.0% Maitake.5 15. cooked (Can) 2.0% 14. boiled (Jap) • 26 Mushroom.0% Shiitake Nama-shiitake.4% Oyster mushrooms boiled (Jap) 3.0% 14.1 Mushroom.3% 25.5% AI for fibre males 19yeas and over equals 30g and for females 19 years and over equals 25g 286 . boiled (Jap) Tree ears.1 Shiitake Hoshi-shiitake boiled (Jap) 7.5 10.7% 16. boiled (Jap) 4. cooked with salt (USDA) 2.6 12.4% Mushrooms. Shiro-kikurage.8% Tree ears.8 16.0% 14.0% 19.2% 12. Arage-kikurage. boiled (Jap) 5. shiitake.6% 16. shiitake.3% 14. shiitake.stir-fried (Can) 3.1 13.6 12.2 17.5 25.4% Winter Mushroom boiled (Jap) 4.3% 65.3% 20.1 Mushrooms.4 21.2% 100g of cooked culinary specialty mushrooms provide an average of 13.0% 18.7% 18.0% 30.Summary Table for COOKED CULINARY SPECIALTY MUSHROOMS providing >10% RDI/AI for fibre /100g Fibre (g) Males 19 years and over Females 19 years and over AI 30 25 Mushrooms Shiitake.7 10.7 12.6 Nameko boiled (Jap) 2. shiitake. Stir fried Lentinus edodes (USDA) 3. cooked without salt (USDA) 2. Kiurage.8% 6.0% Shimeji Bunashimeji boiled (Jap) 4.4% Nutrient Tree ears.

3 1. boiled (Jap) Tree ears.1 RDI 1.4% 30 5.9% 287 .13 10.1% 1.274 21.0% 11.037 0.5 10.2% 27.17 13.0% 13 14.7% 14.1% 10.6 300.0% 15.9% Winter mushroom bottled in seasoning (Jap) 3.1 19.1% 1. cooked without salt (USDA) 0.3% Oyster mushrooms boiled (Jap) 0.4% 13.6 1. Stir fried Lentinus edodes (USDA) 0.5% 13.17 13.6% 3.3 25.274 21.8% 15.12 Shiitake Hoshi-shiitake boiled (Jap) Shiitake Nama-shiitake.1% 17.5% 31.5% 13.5% 13.567 0.6% Winter Mushroom boiled (Jap) 0.1% 24 0.3% 16.0% Shimeji Bunashimeji boiled (Jap) 0.1% 10.0% 10.0% 327.099 0.8% 17.037 0. boiled (Jap) Tree ears.1% 10.19 15.8% 7 43.7% 21 0.6% 15.1% 25 10.2 32.6% 14 11.1 13.1% 1.5% 13.1% 24.9% 17.3% 0.03 0.05 Tr mg 1 0 0.0% 71 15.6% 15. Arage-kikurage.27 20.5% 20.23 17.1% 3.9% 0. boiled (Jap) Tree ears.3 RDI 16 14 RDI 400 400 24.06 Tr mg 2 0 0. shiitake.01 0.19 14.17 13.1% 10. cooked with salt (USDA) 0.Summary Table for COOKED CULINARY SPECIALTY MUSHROOMS providing >10% RDI/AI of key vitamins /100g Nutrient Thiamin (B1) (mg) Males 19 years and over Females 19 years and over Riboflavin (B2) (mg) Males 19-70 years Males over 70 years Females 19-70 years Females over 70 years Niacin equivalents (B3) (mg) Males 19 years and over Females 19 years and over Folate (mcg) Males 19 years and over Females 19 years and over RDI 1.0% 14 4.7 23.6% 28 24.06 0.1% 26.87 Mushrooms.9% 17.6% 63 2.3% 0.4% 22.7% 21 Mushrooms. shiitake.9% 21.2% 21 25.8% 17.8% Mushrooms Shiitake.8% 11. boiled (Jap) 0.8% 50.15 12.8% 3.1% 4.07 0.5 10.6% 15.0% 3.3% 0.12 10.099 0.1 0.1% 4. cooked (Can) Mushroom.2 1.5% 13.0% 27.7 29. Kiurage.3 20.3% 29.4% 39 11.4 27.1 1. Shiro-kikurage.8% 16.1% 15. shiitake.4% 33. boiled (Jap) Mushroom.4% 20.5% 37.037 0.11 Nameko canned in brine (Jap) 0.3% 44 0.1% 24.stir-fried (Can) 11.18 13.7% 2 12.1 1 0.5% 14.6% 11. shiitake.053 Nameko boiled (Jap) 0.06 0.9% 21.8% 17.07 Maitake.17 13.0% 10.8% 10.1% 17.6% 0.6% 23.

0% 1 20. boiled (Jap) Tree ears.0% 26.0% 20.0% 14.0% 20.159 12.7 1.2% 10.5% 2 40.0% 288 20.96 16.0% 620. boiled (Jap) 0.05 17. cooked without salt (USDA) 0.0% 60. boiled (Jap) Mushroom.0% 20.159 12.0% 40.0% 1860.0% 1 20.8% 31.3 1.6% 3.2% 13.04 1. shiitake.594 59.0% 260.06 1.36 22.0% 24.7% Oyster mushrooms boiled (Jap) 0.0% Nutrient Shiitake Hoshi-shiitake boiled (Jap) Shiitake Nama-shiitake.2% 12. Kiurage.0% 14.01 0 39 780.06 2.01 0 15 300.0% 100.0% 22.0% 150.7 14.3% 59.1 1.0% 13.0% 930.3 1.9% 89.0% 390. shiitake. boiled (Jap) Tree ears.09 0.7 14.7 14.6% 1.6% 3.0% 13. boiled (Jap) Tree ears.5% 4 80.5 10.04 17.4% 11.594 59.0% 150.01 0 93 1860. cooked (Can) Mushroom.0% 0.0% 0.2% 10.9 15.6% 3.174 13.2% 12.02 0.0% 10.0% 13.0% 10.9% 0.0% 20. Shiro-kikurage.5% 26.3% 0.stir-fried (Can) 0.7% 29.7% 34.0% Shimeji Bunashimeji boiled (Jap) 0.7% 31. cooked with salt (USDA) 0.174 13.0% 20.0% 30.Summary Table for COOKED CULINARY SPECIALTY MUSHROOMS providing >10% RDI/AI of key vitamins /100g Vit B6 (mg) Males 19-50 years Males over 50 years Females 19-50 years Females over 50 years Pantothenic acid (mg) Males 19 years and over Females 19 years and over Vit D (mcg) Males 19-50 years Males 51-70 years Males over 70 years Females 19-50 years Females 51-70 years Females over 70 years RDI 1.04 0.0% Winter Mushroom boiled (Jap) 0.5 10.0% 14.0% 40.5 AI 6 4 AI 5 10 15 5 10 15 Mushrooms Shiitake.2% 12.9% 0.9% 89.0% 10.24 Nameko canned in brine (Jap) 0.36 39.0% 260.2% 0.3% 40.0% 10.9% 89.0% 0.3% 40.0% 20.0% 620.09 1.0% 13.18 19.0% 10.0% Mushrooms.6% 1.3% 2 40.7% 34.0% 10.0% 30.0% 10.0% 13.25 20.0% 1 20.0% 930.0% 13.52 Maitake.3% 26.7% 80.0% 13.0% 1 20.594 59.3% 40.36 22.0% 13.3% 3 60.09 1.0% 10.4% 10.0% 20.0% 10. shiitake.0% 390.0% 2 40.0% Nameko boiled (Jap) 0.4% 10.0% 100. Arage-kikurage.9% 0.0% 0.0% 20.0% 26.0% Mushrooms.0% 20.0% 20.0% 20.3% 0.0% 0.0% 300.0% 20.2% 10.0% 10.3% Winter mushroom bottled in seasoning (Jap) 0.0% 780.159 12.4% 11. shiitake. Stir fried Lentinus edodes (USDA) 0.0% .

3-620% Tree Ears.9% • Range female 19 and over 13-89. # >10% AI provided by M 13 and F 14 of 17 mushrooms • Range male 19 and over 15–59.9% Mushroom Shiitake.8% 400mcg male and female 19 yars and over Vitamin B6 M 12% F 11. stir fried lentinus Adodes (USDA) and mushrrom Shiitake. stir-fried (Can) providing the greatest amount # >10%RDI provided by M 11 and F 14 of 17 mushrooms • Range male 19 and over – 12.7mg males 50 and over 1.3mg male 19-70: 1.8% • Range female 19 and over – 10.9-327.3mg females19-50: 1.4% • Range female 19 and over – 10.9% 6mg male 19 and over 4mg female 19 and over Vitamin D M and F 163. Shiro-Kikurage.1mg Female 19-70:1.7% F 79.7% F 24.8% 1.6mg men>70 1. shiitake cooked (Can) Provided the greatet amount ## >10% RDI provided by all 17 of 17 mushrooms for M and F * aged 19-50 years • Range male and female 19 –50: 10–1860% • Range male and female 51-70: 10– 930% • Range male and female 70 and over: 13. boilded (Jap) Providing the greatest amount # >10%RDI provided by 5 of 17 mushrooms for M and F • Range male 19 and over – 10.4% F 16.5% 16mg male 19 and over 14mg female 19 and over Folate M and F 14.3mg female>70 Niacin (B3) M 24.4% Mushrooms Shiitake.5mg females 50 and over Pantothenic acid M 30.1mg Female 19 years and over Riboflavin (B2) M 14.9% Mushroom. boilded (Jap) being the greatest contributor providing93 mcg per 100g . stir-fried (Can).5-43. boilded (Jap) Providing the greatest amount # >10%RDI provided by 3 of 17 mushrooms for M and F • Range male and female 19 and over – 11 -17.6-13.7-50% Oyster Mushroom.2– 13.3% 1.8% Oyster Mushroom.1% • Range female 19 and over – 10-24.Table 7 Average %RDI/AI content for each key vitamin /100g Vitamin Average % Recommended Dietary Intake Thiamine (B1) M 72.5% 5mcg Male and female 19-50: 10mcg male and female 51-70: 15mcg male and female >70 289 Comments # >10% RDI provided by 5 of 17 mushrooms for M and F • Range male 19 and over – 10 – 300% • Range female 19 and over – 10.6mg/ 100g. # >10 % RDI provided by M 11 and F 13 of 17 mushrooms • Range male 19 and over – 10 – 21.1% F 42.3mg males 19-50: 1.3% Winter Mushroom bottled in seasoning (Jap) providing 3.5% 1.2mg male 19 years and over 1.

13 3 14.896 52.2% 11.204 240 0. shiitake. boiled (Jap) Tree ears.06 110 11. boiled (Jap) Tree ears. Kiurage.0% 0.7 1.0% 11. Arage-kikurage.7% 13. cooked without salt (USDA) 0.05 3 Nameko canned in brine (Jap) 0.1% 10.896 52.7% 74.08 150 15.03 10 0.07 67 0.204 4 0.7% 29 0.2% 52.7% 29 0.1% 0.163 Mushrooms.stir-fried (Can) 0.896 52.0% 0. shiitake.11 86 0.7% 74.09 43 0.Summary Table for COOKED CULINARY SPECIALTY MUSHROOMS providing >10% RDI/AI of key minerals /100g Copper (mg) Males 19 years and over Females 19 years and over Phosphorus (mg) Males 19 years and over Females 19 years and over Manganese (mg) Males 19 years and over Females 19 years and over Sodium (mg) Males 19 years and over Females 19 years and over AI 1.0% 0.2 RDI 1000 1000 AI 5.0% 15.6% 290 .0% 11.17 89 0.01 11 0.05 2 Shimeji Bunashimeji boiled (Jap) 0.24 2 29 0.5 5 AI 460 460 13.24 1700 Winter Mushroom boiled (Jap) 0. Stir fried Lentinus edodes (USDA) 0.11 2 0.2 10 0.04 39 0.12 10.223 5 52.163 10. Shiro-kikurage.12 2 0.6% 111 Nameko boiled (Jap) 0.7% 74. boiled (Jap) Mushroom.06 110 11.204 4 Mushrooms.53 0.2% 369.6% Nutrient Mushrooms Shiitake.0% 56 0.15 2 Winter mushroom bottled in seasoning (Jap) 0.04 1 Oyster mushrooms boiled (Jap) 0.6% 369. cooked with salt (USDA) 0. boiled (Jap) Mushroom. cooked (Can) Tree ears. shiitake.08 8 Maitake.0% 11.04 11 0. shiitake.223 5 Shiitake Hoshi-shiitake boiled (Jap) Shiitake Nama-shiitake.6% 111 11.1% 9 0.1% 11. boiled (Jap) 0.

6% 0.5% 0. boiled (Jap) 160 0.5 0.1 1.3 0.3 250 0.5 .0% 0.3 10. boiled (Jap) Mushroom.6% 0.7 0.7 326 11.6% 0.53 Nameko boiled (Jap) 10.6 Nameko canned in brine (Jap) 100 0.3 117 24.0% 0.3% 10.5% 0.3% 1.3% 1.1% 291 17. cooked (Can) Tree ears.4 0.53 Nutrient Mushrooms Shiitake.5% 12.3% 0.0% 0. shiitake.8 35.3 10.5 0.stir-fried (Can) 220 0.33 16.44 37 0.8 10.4 Winter mushroom bottled in seasoning (Jap) 320 Winter Mushroom boiled (Jap) 270 Shimeji Bunashimeji boiled (Jap) 340 11.4% 41.5% 21.8 Maitake. cooked with salt (USDA) 117 24. shiitake. Arage-kikurage.5% 0.5 0.44 Shiitake Hoshi-shiitake boiled (Jap) Shiitake Nama-shiitake.6 1 12.8 35. Stir fried Lentinus edodes (USDA) 326 Mushrooms.4% 41.2 1 0.0% 10.33 16.3% 1.4% 12. shiitake. shiitake.0% 210 0.7 79 0. Shiro-kikurage.0% 10. Kiurage.Summary Table for COOKED CULINARY SPECIALTY MUSHROOMS providing >10% RDI/AI of key minerals /100g continued Potassium (mg) Males 19 years and over Females 19 years and over Selenium (mcg) Males 19 years and over Females 19 years and over Zinc (mg) Males 19 years and over Females 19 years and over Iron (mg) Males 19 years and over Females 19-50 years Females over 50 years AI 3800 2800 RDI 70 60 RDI 14 8 RDI 8 18 8 11.7 0.33 16.8 35. boiled (Jap) Tree ears. cooked without salt (USDA) 117 24.4 0.44 Mushrooms.2 0.6% 6. boiled (Jap) Mushroom. boiled (Jap) Tree ears.4% 41.0% 21.4 Oyster mushrooms boiled (Jap) 260 1.96 12.6 0.96 12.6% 6.

cooked (Can) # >10% RDI provided by 5 of 17 mushrooms M and F Range male and female 19 and over – 11-15% Winter mushroom Bottled in seasoning providing the greatest amount.Table 8 Average %RDI/AI content for each Key MINERAL /100g Mineral Average % Recommended Dietary Intake Copper M 42% F 39.4% Female 19 and over range 10.3% Mushroom common Shiitake.8% 1000mg male and female 19 and over Manganese F 10. boiled (Jap) providing the greatest amount #>10% AI for 2 of 17 mushrooms for M and F Winter mushrrom bottled in seasoning providing the greatest amount (Likely seasoning not mushroom) # >10% AI provided for females 19 and over only.3% Tree Ears.7mg male 19 and over 1. With only 4 of the 17 mushrooms contributing to >10%.3% 1. cooked without Salt (USDA) and Cooked with Salt (USDA) and Mushroom common shiitake. Range female 19 years and over – 11.1% Shimeji bunashimeji. # >10% AI provided by 1of 17 mushrooms F only by Tree Ears.2mg Female 19 and over Phosphorous M and F 11. 10-21.2% 14mg Male 19 and over 8mg Females 19 years and over Iron M 13.6% only 5mg female 19 and over Sodium M and F 210% 460mg male and female 19 and over Potassium F 11. cooked without Salt (USDA) and Cooked with Salt (USDA) and Mushroom common shiitake. boiled (Jap) 292 .4-12. Arage-kikurage. cooked (Can) # >10% RDI provided by M 1 and F 6 of 17 mushrooms Range female 19 and over – 12-17.4% F 10. boiled (Jap) Provided the greatest amount # >10% RDI provided by M 3 and F 5 of 17 mushrooms Male 19 and over – 35.7% • Range female 19 and over – 10-74.8% 8mg male 19 and over 18mg female 19 and over 8mg females 51 and over Comments # >10% RDI provided by M 4 and F 7 of the 17 mushrooms • Range male 19 and over – 10-52.5% Oyster mushroom.5 -41.7% only 3800mg male 19 and over 2800mg female 19 and over Selenium M 3% F 5% 70mcg male 19 and over 60mcg female 19 and over Zinc M 10% only F 15. boiled (Jap) providing the greatest amount # >10%RDI provided by 4 of 117 mushrooms for M and F Range for male 19 and over and female over 50.7% Mushroom common Shiitake. kiurage.

10 Maitake dried (Jap) 8. shiitake.7% 46.8% 27.30 Shiitake.18 Mushroom Milk Caps.3% 32. dried (Can) 14.Summary Table for DRIED CULINARY SPECIALTY MUSHROOMS providing >10% RDI/AI for fibre /20g weight Fibre (g) Males 19 years and over Females 19 years and over AI 30 25 27.7 % of the AI27 for fibre for both male and females aged 19 years and over.58 Fungi. dried (Can) 2.1% Nutrient • 27 Mushrooms.3% 32. dried Lentinus edodes (USDA) 2.7% 56. salted (Fin) 0. Cloud ears. AI for fibre males 19yeas and over equals 30g and for females 19 years and over equals 25g 293 .20 Mushroom. dried (Log grown) 1.02 20g of dried culinary specialty mushrooms provide an average of 25. shiitake.30 Shiitake Hoshi-shiitake dried (Jap) 8.

shiitake.9% 33 Shiitake.5% 3.5% 2.3% 13.6% 20.5% 12.06 0.1 RDI 1.0% 48 Mushroom.6% 44 Mushroom Milk Caps.3% 20.20 15.2 1.59 4.5% 14.5% 2. shiitake.9% 23.0% 34.82 17.20 16.0% 11.14 13.1% 33 Shiitake Hoshi-shiitake dried (Jap) 0.1% 19.2% 15.5% 17. dried (Can) 0.1% 91.0% 24. Cloud ears.3 1. dried (Log grown) 0.0% 12.0% 1. dried (Can) 0.2% 0.6 1.5% 18.10 0.4% 2.36 21.4% 7.02 0.9% 29.0% Mushrooms.7% 22.1% 19.5% 24.5% 15.0% 11.5% 21.9% 23.0% 11.82 80.1 1.3 RDI 16 14 RDI 400 400 12.5% 0.06 0.2 10.28 21.08 Fungi.3% N/A Maitake dried (Jap) 0. salted (Fin) 0.25 20.Summary Table for DRIED CULINARY SPECIALTY MUSHROOMS providing >10% RDI/AI of key vitamins /20g weight Nutrient Thiamin (B1) (mg) Males 19 years and over Females 19 years and over Riboflavin (B2) (mg) Males 19-70 years Males over 70 years Females 19-70 years Females over 70 years Niacin equivalents (B3) (mg) Males 19 years and over Females 19 years and over Folate (mcg) Males 19 years and over Females 19 years and over RDI 1.0 0.6% 294 15.7% 18.5% 15.38 29.00 12.4% 12.5% 25.6 .25 19. dried Lentinus edodes (USDA) 0.0% 10.17 1.92 18.25 19.

4% 18.4% 0.4% 39.04 21.19 14.8% 12.9% 15. salted (Fin) 0.38 72.09 1.6% Shiitake Hoshi-shiitake dried (Jap) 0. dried (Log grown) N/A N/A Maitake dried (Jap) 0.Summary Table for DRIED CULINARY SPECIALTY MUSHROOMS providing >10% RDI/AI of key vitamins /20g weight continued Vit B6 (mg) Males 19-50 years Males over 50 years Females 19-50 years Females over 50 years Pantothenic acid (mg) Males 19 years and over Females 19 years and over Vit D (mcg) Males 19-50 years Males 51-70 years Males over 70 years Females 19-50 years Females 51-70 years Females over 70 years RDI 1.7 1.6% Shiitake.7% 12.0% 22.78 15. shiitake. dried (Can) 0.7% Mushroom.8% 11.6% 34. shiitake.2% 18.0% 15.9% 4.0% 34.8% 11.73 56.02 Nutrient 14.2% 10.6% Fungi.10 0 295 22.19 4.3 1.0% 28.06 0.80 56.6% N/A 2.06 21.0% 28.59 26.9% 109. dried (Can) 0.7% 3.7% . dried Lentinus edodes (USDA)+A10 0.9% 109.6% 0.0% 18.2% 10.5 AI 6 4 AI 5 10 15 5 10 15 Mushrooms.40 68.4% 14.4% 14.3 1.7% Mushroom Milk Caps. Cloud ears.38 72.0% 68.0% N/A 1.8% 12.78 15.4% 0.

5% 1.7% Shiitake Hoshi-shiitake.12% Shiitake Hoshie-Shiitake dried (Jap) Proving the greatest amount # >10%RDI provided by all 2 of the 7 mushrooms for M and F • Range male 19 and over – 11.3mg female>70 Niacin (B3) M 26.4 .7 – 20.2.3mg male 19-70: 1.4-109.3mg males 19-50: 1.6mg men>70 1.9% • Range female 19 and over 18.6–68% • Range male and female 51-70: 10.9% F 21.7% • Range female 19 and over – 18.4-14.4% 16mg male 19 and over 14mg female 19 and over Folate M and F 11. Shiitake.8% Maitake dried (Can) and Mushrooms.2-72.22.5% Maitake dried (Jap) providing the greatest amount # >10% RDI provided by all 6 of the 7 listed mushrooms for M and F • Range male 19 and over – 10.4% 1.5% 400mcg male and female19 and over Vitamin B6 M 13.6% Maitake dried (Jap) Proving the greatest amount # >10%RDI provided by all 2 of 7 mushrooms for M and F • Range male and female 19 and over – 11 .80.91.1% F 69.6-34% • Range male and female 70 and over: 18.9-14.9% Maitake dried (Jap) Proving the greatest amount # >10%RDI provided by all 6 of the 7 listed mushrooms for M and F • Range male 19 and over – 10 .1mg Female 19 years and over Riboflavin (B2) M 17.7% F 20.7 -22.5mg females 50 and over Pantothenic acid M 46.6 % F 30.5% • Range female 19 and over – 13-34.3mg females19-50: 1.7mg males 50 and over 1.Table 9 Average %RDI/AI content for each Key Vitamin /20g Vitamin Average % Recommended Dietary Intake Thiamine (B1) M18. Shiitake.9% 1.2% 6mg male 19 and over 4mg female 19 and over Vitamin D M and F 29% 5mcg Male and female 19-50: 10mcg male and female 51-70: 15mcg male and female >70 296 Comments # >10%RDI provided by 2 of 7 mushrooms for M and F • Range male 19 and over – 16. dried (Fin) being the greatest contributor providing 3.8% • Range female 19 and over – 12. dried Lentinus edodes (USDA) Proving the greatest amount # >10% AI provided by 4 of 7 mushrooms for M and F • Range male 19 and over 12.2mg male 19 years and over 1. dried Lentinus edodes (USDA) Proving the greatest amount # >10% RDI provided by 5 of 7 mushrooms for M and F • Range male and female 19 –50: 15.1mg Female 19-70:1.1% F 13.6 -29.4% Maitake dried (Can) and Mushrooms.4mcg per 100g .1% • Range female 19 and over – 11.

shiitake.8 11.04 36.7% 140 14. shiitake.10 62 1.1% 13.03 58. dried (Can) 1.Summary Table for DRIED CULINARY SPECIALTY MUSHROOMS providing >10% RDI/AI of key minerals /20g weight Copper (mg) Males 19 years and over Females 19 years and over Phosphorus (mg) Males 19 years and over Females 19 years and over Sodium (mg) Males 19 years and over Females 19 years and over Potassium (mg) Males 19 years and over Females 19 years and over AI 1. dried (Can) 0.0 Nutrient 60.0% 297 42.2% 15.8 7.7 1.9% 86.8 11.0% Maitake dried (Jap) 0. dried Lentinus edodes (USDA) 1.03 60.0% 17.8% 20.1% 29.7% 68 150.9% .0% 14.1% 58.4 196. Cloud ears.7% 42. salted (Fin) N/A 14.6 306.0% 11.2 420 Mushroom.8 2.2 RDI 1000 1000 AI 460 460 AI 3800 2800 Mushrooms.6 500 Mushroom Milk Caps.8 11.8 2.6 306.0% Shiitake.8 Shiitake Hoshi-shiitake dried (Jap) 0.6 306.8% 86.36 0.6 Fungi. dried (Log grown) N/A 48 2.

2% 0.78 17.34 0.46 13.34 Shiitake Hoshi-shiitake dried (Jap) N/A Mushroom.22 Shiitake.Summary Table for DRIED CULINARY SPECIALTY MUSHROOMS providing >10% RDI/AI of key minerals /20g weight Selenium (mcg) Males 19 years and over Females 19 years and over Zinc (mg) Males 19 years and over Females 19 years and over Iron (mg) Males 19 years and over Females 19-50 years Females over 50 years RDI 70 60 RDI 14 8 RDI 8 18 8 Mushrooms. dried (Log grown) N/A N/A Maitake dried (Jap) N/A 1. shiitake.4% 14.68 12.14 0.18 Nutrient 0.3% 298 0.4% 1.52 14.34 10.54 Fungi.4% 1.5% 0.26 1.53 10. dried (Can) 9.2% 0.2% 15.3% 12.0% 0.53 0. Cloud ears. shiitake. salted (Fin) 7.9% 19.9% 19. dried (Can) 8.7% 14.2% 15.7% .2 10. dried Lentinus edodes (USDA) 9.38 Mushroom Milk Caps.22 13.

7% Mushroom.86.2% Mushrooms. milk caps. Shiitake dried Lentinus edode (USDA) Mushrooms.5% F 67.3% 1. Shiitake dried (Can) providing the greatest amount # >10 % RDI provided by 1 of 7 mushrooms for M and F # 14.Table 10 Average %RDI/AI content for each key mineral /100g Mineral Average % Recommended Dietary Intake Copper M 47.2mg Female 19 and over Phosphorous M and F 14% Only 100mg male and female 19 and over Sodium M and F 42.3% 70mcg male 19 and over 60mcg female 19 and over Zinc M 10. dried (Can) providing the greatest amount providing the greatest amount #>10% RDI provided by M 2 and F 3 of 7 mushrooms • Male 19 and over – 10.1% Shiitake Dried Lentinus edodes (USDA) and Mushroom. shiitake.7% only 460mg male and female 19 and over Potassium M 12.9% Maitake dried (Jap) Providing the greatest amount.3-19.4% Shiitake Dried Lentinus edodes (USDA) and Mushroom. dried (Can) providing the greatest amount # >10% RDI provided by 1of 7 mushrooms for M and F • Male and female 19 and over – 14% Maitake dried (Jap) providing the greatest amount # >10% AI provided by 1 of 7 mushrooms for M and F • Male and female 19 and over 42. Nil other provided >10% AI for sodium # >10 % AI provided by 2 of 7 mushrooms for M and F • Range male 19 years and over 11.7 % RDI provided by • Fungi cloud ears dried (Can) containing 1.9 – 60.1-13.18mg/20g 299 .2% • Range female 19 years and over – 11-17.3-13.1% 3800mg male 19 and over 2800mg female 19 and over Selenium M 4.9% • Range female 19 and over – 17.9% only F 18. # >10 % RDI provided by 3 of 7mushrooms • Range male 19 and over – 10.1% F 13.8% • Range female 19 and over – 29.5% 14mg males 19 years and over 8mg Females 19 years and over Iron M and F 14.7mg male 19 and over 1.2% • Range female 19 and over – 12 -15. salted (Fin) providing the greatest amount. shiitake.7 .3% F 14.7% 8mg male 19 and over 18 female 19-50 : 8mg females 51 and over Comments # >10% AI provided by 3 of 7 mushrooms for M and F • Range male 19 and over – 20.

. but not in pre-menopausal women (Hong et al. 2006). and a strong inverse association was found in postmenopausal women. An epidemiological study of women with histologically confirmed breast cancer has identified that daily intake and the average consumption frequency of mushrooms were inversely associated with breast cancer risk. the lowest quartile intake. greater mushroom intake was related to lower risk of breast cancers among premenopausal women for the highest vs. A subsequent reduction in estrogen..tumors.. 2012b). described in both in vitro and animal trials (Grube et al. suggesting that this effect may be more robust among women with hormone receptor positive tumors. and Maitake (Grifola frondosa) mushrooms (Xu et al. The use of mushrooms as anti-cancer therapeutics has also recently been reviewed (Patel and Goyal..1. and the association may be more robust among women with hormone receptor positive tumours (Aesun et al. 2011a). 2001. which is in contrast to another epidemiological study that has suggested a decreased risk of breast cancer from mushroom consumption by pre-menopausal women (Shin et al. and more recently in a human trial of postmenopausal women diagnosed with breast cancer (Palomares et al.mushrooms (Pleurotus ostreatus). 2012. 2012. The results suggest that high consumption of mushrooms may be related to a lower risk for breast cancer among premenopausal women. Soumya et al. 2008). Petrova.1 Breast Cancer A recent clinical trial with Korean women has evaluated the association between mushroom intake and the risk of breast cancer according to hormone receptor status. 5.. 2010). affecting estrogen receptor positive tumors was reported in animal trials. Mushroom intake and breast cancer risk were examined among 358 breast cancer patients and 360 cancer-free controls.1.. The association was stronger for premenopausal women with estrogen receptor (ER)+/progesterone receptor (PR) + tumors than those with ER-/PR.. Greater mushroom intake was related to lower risk of breast cancers among premenopausal women with the association being stronger for premenopausal women with estrogen receptor (ER)+/progesterone receptor (PR)+ tumours than those with ER/PR tumours. Intake of mushrooms was assessed using a quantitative food frequency questionnaire. Chen et al.. 2011). 2011) for Agaricus bisporus. In this latter study. A possible mechanism for this effect may be via an inhibition of aromatase activity.. 2010). Recent evidence suggests that the anti-aromatase compound in Agaricus bisporus is conjugated linoleic acid (CLA) (Kanaya et al. 40 . Shiitake mushrooms (Lentinus edodes). 2012).. as have the levels of evidence from human trials of mushroom intake (Roupas et al.

which is supported by an animal model study that has reported that the major active compounds (in Agaricus bisporus) are unsaturated fatty acids such as linoleic acid..and postmenopausal women and an additional decreased risk of breast cancer was observed from a synergistic effect of mushrooms and green tea in a case-controlled study (Zhang et al. PSK).. 2006). extracted from Coriolus versicolor strain CM-101. and several studies have shown that mushroom extracts are able to suppress the proliferation of breast cancer cell lines.. Jin et al.. without affecting the proliferation of normal (non-cancer) cell lines (Israilides et al. 2006). An in vitro study using an aqueous extract of Agaricus bisporus has identified suppression of aromatase activity and estrogen production as key mechanisms (Grube et al.. 2009).cells. Coprinus comatus. 2009). Suppression of the transcription factors NF-kappaB and AP-1 has also been demonstrated by Ganerderma lucidum (Thyagarajan et al. 2006. regardless of the hormone receptor status of the cancer cells (Gu and Leonard.. Polysaccharide K (Krestin. Studies in animal models and human cell lines have provided insights into the possible mechanisms involved for the effects of mushrooms and their components on breast cancer. These activities were dose-dependent. with a suggestion that the active components in mushrooms in these effects may be hydroxylated triterpenes (Jiang et al. 2008). and significantly inhibited MCF-7 tumor colony formation in vitro. an in vitro study using water-based extracts of Coprinellus sp. Flammulina velutipes.. it should be noted that they were not direct intervention trials and mushroom consumption was assessed via quantitative food frequency questionnaires.However. While these human trials are promising. Jiang et al. Higher dietary intake of mushrooms decreased breast cancer risk in both pre. 2006). Vitamin D2 could be one of the protective phytonutrients against breast cancer as mushrooms are rich in ergosterol. linolenic acid. Jedinak and Sliva. significantly inhibited growth of both estrogen-receptor positive (ER+) and estrogen-receptor negative (ER-) breast cancer cells. 2008). 2001). is a nonspecific immunomodulatory polysaccharide which induces interleukin 2 (IL-2) and interferon 41 . 2004a. which can be affected by recall bias. Inhibition of proliferation of human breast cancer cell lines has also been suggested to be mediated via downregulation of Akt/NF-kappaB (transcription factor) signalling in several mushroom varieties (Jiang et al. and CLA which have been shown to inhibit aromatase activity (Chen et al. 2008). generating vitamin D2 when exposed to ultraviolet B (UVB) light and ergocalciferol being bioavailable and increasing serum 25(OH) vitamin D2 levels in humans (Furlanetto.. induction of rapid apoptosis on both ER+ and ER... 2008.

as well as in the quality of life of breast cancer patients (Novaes et al.. alanine aminotransferase. flatus retention.. double-blind.. Oral administration of PSK has been shown to significantly inhibit breast cancer growth in tumor-bearing neu transgenic mice (Lu et al. pyrosis. indicators which were not observed in the placebo group (Fortes et al. reduced complaints of pain and reduced alterations of sleep such as insomnia and restless sleep. postprandial fullness. thereby stimulating lymphokine activated killer cells and enhancing natural killer cells (Sakamoto et al. The data suggest that dietary supplementation with Agaricus sylvaticus was capable of providing metabolic benefits to the biochemical. IgM.1. 2012). flatulence. aspartate aminotransferase. total cholesterol. with the indication that PSK is a specific Toll-like receptor 2 (TLR2) agonist and exerts its anti-tumor effects via stimulation of both innate and adaptive immune pathways..(IFN) γ. IgA. systolic blood pressure and diastolic blood pressure. reduced constipation. creatinine. 2006). The effects of PSK in cancer therapy and the possible mechanism of action have recently been reviewed (Sun et al. abdominal distention and abdominal pain. diarrhea. placebo-controlled clinical trial carried out in Brazil over a six month period with 56 patients has studied life quality of postsurgical patients with colorectal cancer after supplementation of the diet with Agaricus sylvaticus (30 mg/kg/day).2 Colorectal Cancer A randomized. 2011). enzymatic and blood pressure parameters of these patients with colorectal cancer in the postsurgical phase (Fortes and Novaes.1. The supplemented group also presented with increased appetite. After six months of treatment. Polysaccharide krestin (PSK). A further evaluation of the same patients reported that the Agaricus sylvaticus group had significantly reduced fasting plasma glucose. 2008).. 2010). nausea. an extract from Trametes versicolor. the supplemented group had increased physical activity.. alternate diarrhea/constipation. improved disposition and mood. Mushroom polysaccharopeptides have also been implicated in apoptopic effects in human breast cancer cell lines (Wan et al. 2011). A review of the use of mushrooms as adjuvant treatments in breast cancer has reported that mushroom intake is associated with improvements in the immunological and hematologic parameters of breast cancer. 42 . has been reported to reduce toxicity of current treatments used in patients with metastatic colorectal cancer (Shibata et al. 2011). 2011c).. 5. all effects that were not observed in the placebo group.

.. It has been suggested that the pro-apoptotic effects in HT-29 cells is induced by an increase in the activity of caspase-3 (Hong et al. 2009).. but not in a normal. 1993) and other mushrooms have reported pro-apoptotic effects with no associated cytoxicity. although intake of 5% Ab over 4 weeks by male Wistar rats did not confirm chemopreventive activity on the initiation stage of rat colon carcinogenesis (Ziliotto et al. 2006). twice daily (30mg/kg/day). Ziliotto et al. Agaricus bisporus lectin (ABL) (Yu et al. not double-blind or placebo controlled) evaluating water-soluble G. healthy population. More recent studies have suggested the pro-apoptotic effects and inhibition of the growth of HT-29 colonic cancer cells is mediated through up-regulation of the expression of pro-apoptotic proteins and down-regulation of anti-apoptotic proteins (Lee et al.. 2009c). placebo-controlled. 2005). lucidum polysaccharides (Ganopoly®) in patients with advanced colorectal cancer reported that treatment with Ganopoly® tended to increase mitogenic reactivity to phytohemagglutinin. 2011).. 2004). A randomized..Two meta-analyses of randomised clinical trials have suggested that adjuvant immunochemotherapy with polysaccharide K from mushrooms can improve the survival of and disease-free survival of patients with curatively resected colorectal cancer (Oba et al... Larger double-blind trials are required to validate this effect and further studies are needed to determine the mechanism of action. These data suggest that mushrooms may have an immunostimulatory effect on immunocompromised patients. 2007.e. The inhibition of proliferation has been shown to be reversible after removal of 43 . A clinical study of healthy volunteers reported that Ganoderma lucidum did not affect their immune functions. for six months also suggested benefits in haematological and immunological parameters and reduced glycemic levels in patients with colorectal cancer (Fortes et al. The mechanism of this effect is possibly via action of PSK on a toll-like receptor initiating a signalling cascade involving T helper 1 cells which induce IL-2 and IFN-γ and then activate natural killer cells. This sequence of signalling cascades has recently been described in the modulation of innate immunity of Agaricus blazei (Ab) (Hetland et al. orally. 2008.. 2004). efficacy.. double-blind clinical trial in which patients with colorectal cancer were supplemented with Agaricus sylvaticus mushroom.. but a subsequent open-labeled study (i. Several in vitro studies in HT-29 human colonic carcinoma cells with extracts from Ganoderma lucidum (Hong et al. 2009).. The reduction of death rate by 29% and of recurrence by 28% by PSK immunochemotherapy over standard oral fluorinated pyrimidine based chemotherapy may have been due to restoration of immunity in patients who could have been immunosuppressed due to surgery and chemotherapy (Sakamoto et al.lucidum polysaccharides in cancer patients (Gao et al. and safety of the water-soluble G. Sakamoto et al. 2006).

2004). 2000). 2006). 2008) and pro-apoptotic effects (Shomori et al. and endometrial cancer patients were treated either with carboplatin plus VP16 or with carboplatin plus taxol every 3 weeks for at least three cycles. and general weakness were all reported to be improved by ABMK treatment (Ahn et al. no significant difference in lymphokine-activated killer and monocyte activities was observed.4 Gastric Cancer A meta-analysis of the effect of immunochemotherapy with lentinan compared to chemotherapy alone has been evaluated in patients with advanced gastric cancer across five randomised controlled trials. One hundred cervical. Chen et al.. Natural polysaccharides isolated from Phellinus gilvus (PG) have been shown to decrease cell proliferation and increase cell apoptosis in a dose-dependent manner in vitro in a model of human gastric adenocarcinoma and also to lead to a marked inhibition of tumor growth and a significant decrease in the incidence of peritoneal carcinomatosis (Bae et al. 2006) (Shomori et al. on immunological status and quality of life has been studied in cancer patients undergoing chemotherapy. 2009).. 44 .. Very little is known about the mechanisms involved in the effects of mushrooms or mushroom extracts in cervical. ovarian and endometrial cancers.. However.1.. Ovarian. Chemotherapy-associated side effects such as appetite loss.dependent (Jin et al.1. 2008a). 2010d) via an induction of apoptosis (Ren et al. ovarian... 5.3 Cervical. Lentinan significantly prolonged overall survival but was possibly more effective in patients with lymph-node metastasis than in non-node metastasis patients (Oba et al..1. with or without oral consumption of ABMK. emotional instability. 2009) in human gastric cell lines also were reported for several mushroom extracts with both caspase-3 . 2009) and independent signalling cascades being implicated (Shomori et al. The authors observed that natural killer cell activity was significantly higher in the ABMK-treated group compared to the non-treated placebo group (n = 61).(Agaricus bisporus) lectin (Yu et al. with only a small number of reports suggesting anti-proliferative effects (Liu et al.....1. 2009. Endometrial Cancer The effect of consumption of an extract from Agaricus blazei Murill Kyowa (ABMK).. 2009). Antiproliferative (Chen et al. 1993) and the reversibility of the anti-proliferative effect was associated with the release of the lectin from cancer cells after internalization (Yu et al. alopecia. 5.

5 g/day for 6 months) in 74 patients with early stage prostate cancers. 5. containing the Ganoderma lucidum mushroom has reported no serious adverse effects..5. A 6 month open-label study in 51 patients with prostate cancer that ingested either Senseiro.1.1. 2002) showed no effect on prostate-specific antigen levels in patients with either lower urinary tract symptoms or patients with prostate cancer respectively. or Rokkaku Reishi. containing extracts from the Agaricus blazei Murill mushroom. 45 .. The preliminary anti-tumor activity documented in a patient with advanced pancreatic cancer and the positive pre-clinical anti-tumor effects observed on intermittent dosing schedules support a need for further trials on irofulven.64mg/m2) as a 5-minute intravenous infusion daily for 5 days every 4 weeks. A Phase I trial and pharmacokinetic study of irofulven.5 Pancreatic Cancer / Solid Malignancies Only one single trial on the effects of a mushroom-derived compound on pancreatic cancer in humans has been reported. It should be noted that the source of this compound (Omphalotus olearius) is not an edible mushroom (Eckhardt et al. Patient ingestion compliance was maintained near 100% during the course of the trial. While the highest dose used was not well tolerated (grade 4 neutropenia and renal toxicity).1. 2008a. 2010)... A Phase II clinical trial has assessed the efficacy and safety of mushroom mycelium extracts (4. the authors recommended a lower dose of irofulven (10.1.6 Prostate Cancer Human trials to date have shown that mushrooms and their extracts to be ineffective in the treatment of clinical prostate cancer. The mushroom mycelium extract was an ineffective treatment for reducing 50% or more the patient prostate specific antigen values (Sumiyoshi et al. a mushroomderived cytotoxin has been carried out in 46 patients with advanced solid malignancies. 2010). and no significant anticancer effects were observed with the intake of these two mushroom supplements (Yoshimura et al. Noguchi et al. 2000)... Trials with Ganoderma lucidum (Noguchi et al. 2008b) and with a polysaccharide/oligosaccharide complex obtained from a Shiitake mushroom extract (White et al. although the treatments have been well-tolerated.

the TCA cycle and immune responses (Adams et al. 46 . The mechanisms by which mushrooms and their extracts affect prostate cancer cells appear to be multi-modal with gene network analysis of studies with Agaricus bisporus identifying alterations in networks involved in apoptosis. In other human trials. lipid metabolism. The data showed that the Shiitake mushroom extract alone was ineffective in the treatment of clinical prostate cancer (White et al.. resulting in the down-regulation of secretion of vascular endothelial growth factor and transforming growth factor beta (TGF-beta1) from PC-3 cells. where several mushrooms and their extracts have been reported to inhibit proliferation of human prostate cancer cell lines. 2009a). These human trial outcomes do not support in vitro mechanistic studies. 2010). 2010)... with activities of caspase 3 and DNA fragmentation being enhanced the most in androgen-independent PC3 cells (Yu et al..Supplemental amounts of a polysaccharide/oligosaccharide complex obtained from a Shiitake mushroom extract have been evaluated for the ability to lower the prostate-specific antigen level in patients (n=62) with prostate cancer. Beta-glucan from Grifola frondosa (Maitake) has a cytotoxic effect on human androgen-independent prostatic cancer PC3 cells in vitro. Inhibition of proliferation in a dose.. 2005). 2002). 2000). An Agaricus blazei extract (with a high ratio of beta-glucan) inhibited cell proliferation in both androgen-dependent and androgen-independent prostate cancer cell lines via an apoptotic pathway. and G. while a recent study has also suggested that a Phellinus linteus extract is able to sensitize advanced prostate cancer cells to apoptosis in athymic nude mice (Tsuji et al.. leading to apoptosis (Fullerton et al. lucidum inhibits prostate cancer-dependent angiogenesis by modulation of MAPK (mitogen activated protein kinase) and Akt signaling (Stanley et al. 2008)...and time-dependent manner and induction of apoptosis in PC-3 human prostate cancer cells by Ganoderma lucidum (Jiang et al. 2010). (containing the Ganoderma lucidum mushroom) for 6 months in patients with prostate cancer also failed to show a response in terms of serum prostate-specific antigen (Yoshimura et al. 2004b) has been determined to be caused by the inhibition of constitutively active AP-1 in prostate cancer cells. while a Phase II human trial of 74 early prostate cancer patients reported a mushroom mycelium extract to be ineffective in reducing by 50% or more the patient prostate specific antigen values (Sumiyoshi et al. treatment with Senseiro (containing extracts from Agaricus blazei Murill) and Rokkaku Reishi. growth and proliferation..

5.1.2 Anti-Microbial Properties
Anti-microbial effects of a large number of mushroom varieties and mushroom components on
both gram-positive and gram-negative bacteria have been confirmed via in vitro studies. A small
number of animal studies have been undertaken and the data suggest that the anti-microbial
effects in vivo may be mediated by effects on the immune system. Initial studies in humans
suggested anti-microbial properties of extracts from Agaricus blazei Murill and Ganoderma
lucidum, although these studies did not have adequate controls in the experimental design, and
therefore such effects have not yet been scientifically validated in humans.
Patients on dialysis are at high risk of infection, including fungal infections. Anti-beta-glucan
antibody participates in the immune response to fungal cell wall beta-glucan. The anti-betaglucan antibody titer has been shown to be lower in dialysis patients than in healthy volunteers,
and long-term dialysis patients showed lower anti-beta-glucan antibody titers than short-term
dialysis patients. The titer of anti-beta-glucan antibody as a recognition molecule of beta-glucan
was low in dialysis patients compared to healthy volunteers, which may in part explain the
sensitivity to infection of dialysis patients. Although not proven, there is a possibility that
mushroom consumption may assist in a preventative role for fungal infection in dialysis patients
(Ishibashi et al., 2011).
A prospective controlled trial in humans (n=52) has evaluated the in vivo efficacy of the
mushroom Tremella mesenterica Ritz.:Fr. (higher Basidiomycetes) on eradication of
Helicobacter pylori. Ten-day treatment was not found to be effective in vivo in eradicating
Helicobacter pylori, whether given with or without omeprazole, although the brief treatment
period was a limitation of the study (Lachter et al., 2012).
A very small one-year open-label (not double-blind or placebo-controlled) pilot study reported
that intake of Agaricus blazei Murill (AbM) extract (1500 mg daily) over 12 months improved
liver function in patients with hepatitis B, determined by a decrease in the mean level of
aspartate aminotransferase and alanine aminotransferase decreased from 246.0 to 61.3 IU/L
and 151.0 to 46.1 IU/L, respectively (Hsu et al., 2008a). The initial observation seems to
indicate a potential benefit of AbM extract in normalizing liver function of patients with hepatitis
B, although clearly larger and controlled studies are required to confirm such effects.

47

5.1.3 Anti-Viral Properties
Proteins, peptides and polysaccharopeptides from mushrooms have been reported to inhibit
human immunodeficiency virus type 1 (HIV-1) reverse transcriptase and protease, the two
enzymes of importance to the life cycle of HIV. Inhibitory effects on hepatitis B and herpes
simplex virus type 1 have also been reported. The anti-viral effects of mushrooms do not seem
to be related to viral adsorption or virucidal effects (i.e. they do not kill the virus), however a
number of studies have reported inhibitory effects at the initial stage of virus replication (Faccin
et al., 2007).
Two phase I/II placebo-controlled trials in 98 HIV-positive patients were completed using
lentinan, a β-glucan isolated from Lentinus edodes (Shiitake mushroom) (Gordon et al., 1998).
The studies reported generally good tolerability of lentinan with observed side effects being
mainly mild, particularly when infusion was carried out over a 30 minute period. In the first study,
where administration was over a 10 minute period, there were 9 side effects severe enough to
be reported to the FDA (one case each of anaphylactoid reaction, back pain, leg pain,
depression, rigor, fever, chills, granulocytopenia and elevated liver enzymes) with four patients
discontinuing therapy because of side effects. In the second study, where infusion was over a
30 minute period, there were no side effects reportable to the FDA but there were four drop-outs
due to side effects or personal preference. Most side effects resolved promptly after the
discontinuation of medication, and all of them were relieved within 24 hours. The small number
of patients in the study groups meant the data on possible increases in CD4 cell and neutrophil
activity were inconclusive (Gordon et al., 1998).

5.1.4 Asthma
A Cordyceps extract has recently been evaluated in asthmatic children during remission stage
(Sun et al., 2010). The Cordyceps extract inhibited the proliferation and differentiation of Th2
cells and reduced the expression of related cytokines by down-regulating the expression of
GATA-3 mRNA and up-regulating the expression of Foxp3 mRNA in peripheral blood
mononuclear cells. The extract was able to alleviate the chronic allergic inflammation by
increasing the level of interleukin-10.

48

5.1.5 Cardiovascular Health
A human intervention study has evaluated the cholesterol lowering properties of an Oyster
mushroom (Pleurotus ostreatus) diet. Twenty subjects (9 male, 11 female; 20-34 years) were
randomized to take either one portion of soup containing 30 g dried oyster mushrooms or a
tomato soup as a placebo daily for 21 days. The Oyster mushroom soup decreased
triacylglycerol concentrations (0.44 mmol/L) and oxidized low density lipoprotein levels (7.2
U/mL) significantly, and showed a significant tendency in lowering total cholesterol values (0.47
mmol/L; p = 0.059). No effects on low density lipoprotein and high density lipoprotein levels
were observed (Schneider et al., 2011).
Oyster mushroom consumption by 89 diabetic patients significantly reduced systolic and
diastolic blood pressure, total cholesterol and triglycerides, with no significant change in body
weight and no deleterious effects on liver or kidney function (Khatun et al., 2007). Another study
in 90 female volunteers demonstrated a weight-controlling and hypolipidemic effect of proteinbound polysaccharides from the mycelia of Agaricus blazei and Lentinus edodes, via a
mechanism involving absorption of cholesterol (Kweon et al., 2002). However, a double-blind,
placebo-controlled, cross-over intervention study in adults (n=18; ages 22–52 years) of a
commercially available encapsulated Lingzhi preparation (equivalent to 13.2g fresh
mushroom/d) over 4 weeks failed to show any change in biomarkers for coronary heart disease
risk (Wachtel-Galor et al., 2004).
The bioavailability of ergothioneine from Agaricus bisporus, that functions as an antioxidant in
mushrooms has been determined in a pilot study in healthy men (n=10) using a randomized,
cross-over, dose-response, postprandial time-course design. Ergothioneine was bioavailable
after consuming mushrooms (8g and 16g) and a trend in the postprandial triglyceride response
indicated that there was a blunting effect after both the 8g and 16g ergothioneine doses were
compared with the control (0g dose). Ergothioneine from A. bisporus mushrooms was therefore
bioavailable as assessed by red blood cell uptake postprandially, and consumption was
associated with an attenuated postprandial triglyceride response (Weigand-Heller et al., 2012).
A single-arm, open-label, proof-of-concept study of 8 weeks duration has been completed
which assessed the safety and efficacy of Pleurotus ostreatus (15 g/day orally) in HIV-infected
individuals taking antiretroviral therapy that induced hyperlipidemia. Pleurotus ostreatus at the
concentration taken in this study did not lower non-HDL cholesterol in HIV patients with
antiretroviral treatment-induced hypercholesterolemia. Small changes in HDL and triglycerides
were not of a clinical magnitude to warrant further study (Abrams et al., 2011). The effects of

49

mushroom consumption on biomarkers of cardiovascular disease risk have recently been
reviewed (Guillamon et al., 2010).

5.1.6 Cognition / Brain Health
Although preliminary, data showing protective effects of mushrooms (Hericium erinaceum) on
beta-amyloid peptide toxicity (Kawagishi and Zhuang, 2008) in the brain and mild cognitive
impairment (both precursors to dementia) appeared promising. Preliminary human trials with
Hericium erinaceum derivatives showed efficacy in patients with dementia in improving the
Functional Independence Measure (FIM) score or retarding disease progression (Kawagishi and
Zhuang, 2008), while a double-blind, parallel-group, placebo-controlled trial with oral
administration of Yamabushitake (Hericium erinaceus) to 50 to 80-year-old Japanese men and
women diagnosed with mild cognitive impairment reported significantly increased cognitive
function scores compared to placebo during intake, but the scores decreased significantly
following termination of the intake (Mori et al., 2009).
A large epidemiological study (The Hordaland Health Study) of 2031 elderly subjects (aged 7074 years; 55% women) recruited from the general population in Western Norway has examined
the relationship between intake of different plant foods and cognitive performance in elderly
individuals in a cross-sectional study design. The cognitive test battery covered several
domains (Kendrick Object Learning Test, Trail Making Test - part A, modified versions of the
Digit Symbol Test, Block Design, Mini-Mental State Examination and Controlled Oral Word
Association Test). A validated and self-reported food frequency questionnaire was used to
assess habitual food intake. Subjects with intakes of >10th percentile of fruits, vegetables, grain
products and mushrooms performed significantly better in cognitive tests than those with very
low or no intake, with the dose-dependent association being linear for mushrooms (Nurk et al.,
2010).
A case-controlled study of 249 patients with diagnosed Parkinson’s Disease (PD) and controls
without neurodegenerative diseases (n = 368) has assessed dietary intake during the preceding
1 month using a validated, self-administered diet history questionnaire. Three dietary patterns
were identified: 'Healthy', 'Western' and 'Light meal' patterns. After adjustment for potential nondietary confounding factors, the Healthy pattern, characterized by a high intake of vegetables,
seaweed, pulses, mushrooms, fruits and fish, was inversely associated with the risk of PD with
a border-line statistical significance (P = 0.06). No associations with PD were detected for the
other two dietary patterns (Okubo et al., 2011). While the data from this case-control study
suggest a dietary pattern consisting of high intakes of vegetables, seaweed, pulses,

50

mushrooms, fruits and fish may be associated with a decreased risk of PD, the strength of the
association is modest and any such effects would need to be confirmed in other studies with
greater statistical power in the study designs.
A human study of 30 females has investigated the clinical outcomes of 4 weeks of intake of
Hericium erinaceus cookies versus placebo cookies 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 (PSQ1),
and the Indefinite Complaints Index (ICI). Each of the CES-D and the ICI score after the H.
erinaceus intake was significantly lower than at the start of the trial. "Concentration", "irritating"
and "anxious" tended to be lower than the placebo group (Nagano et al., 2010, Shimizu et al.,
2010). While the results point towards a possible reduction of depression and anxiety in the
study group with H. erinaceus intake, larger studies with greater statistical power are required
to confirm such outcomes.

5.1.7 Constipation
Constipation is one of the most prevalent gastrointestinal complaints and high fiber intake is
recommended as an initial therapy for constipation. Ear mushrooms (Auricularia) are known to
have higher fiber contents (by ~50%) than other mushroom varieties. In patients with functional
constipation, fiber supplements using ear mushrooms have been shown to significantly improve
constipation related symptoms without serious side effects (Kim et al., 2004b).

5.1.8 Dental Health
A clinical trial in 30 volunteers has been undertaken over 11 days in which a low molecular
mass (LMM) fraction of an aqueous extract of Lentinus edodes (Shiitake) was evaluated as an
oral mouthrinse. The mushroom extract was evaluated against Listerine and a placebo (water).
Statistically significant differences were obtained for the plaque index on day 12 in subjects
treated with mushroom versus placebo, while for the gingival index significant differences were
found for both mushroom versus placebo and mushroom versus Listerine. Decreases in total
bacterial counts and in counts of specific oral pathogens were observed for both mushroom
extract and Listerine in comparison with placebo. The data suggest that this mushroom extract
may prove beneficial in controlling dental caries and/or gingivitis/periodontitis (Signoretto et al.,
2011). A fraction from Shiitake has also been shown to have a strong inhibitory effect on dentin

51

demineralization and induce microbial shifts that could be associated with oral health (Zaura et
al., 2011).

5.1.9 Diabetes
A large number of animal studies, using both normal and diabetic animals, have demonstrated a
hypoglycaemic effect of mushrooms and mushroom components. This effect appears to be
mediated via mushroom polysaccharides (possibly both α- and β-glucans) via a direct
interaction with insulin receptors on target tissues, although this mechanism remains to be
confirmed.
A randomized, double-blinded, and placebo-controlled clinical trial (n=72) showed that Agaricus
blazei Murill supplementation in combination with metformin and gliclazide improved insulin
resistance in these subjects. An increase in adiponectin concentration after Agaricus blazei
Murill extract consumption for 12 weeks may be the mechanism that resulted in the reported
effect (Hsu et al., 2007). Clinical investigation in diabetic patients (n=89) has also shown that
Oyster mushroom consumption significantly reduced systolic and diastolic blood pressure,
lowered plasma glucose, total cholesterol and triglycerides significantly, with no significant
change in body weight, and no deleterious effects on liver or kidney function (Khatun et al.,
2007). These results in humans mirror the decreases in plasma glucose, cholesterol and
triglyceride concentrations following Agaricus bisporus consumption observed in rats (Jeong et
al., 2010) and the reduction in blood pressure in Zucker fatty rats following oral administration of
Maitake mushroom fractions (Talpur et al., 2002).
The consistency between the effects of the mushroom extracts in diabetic animal models
described later in this report and preliminary data from human trials, which mirror decreases in
plasma glucose, blood pressure, cholesterol and triglyceride concentrations, strengthens the
level of evidence for anti-diabetogenic effects of the studied mushrooms and their extracts.

5.1.10 DNA Damage
The antioxidant properties of Ganoderma lucidum (Lingzhi or Reishi) and its effects on DNA
damage and repair in lymphocytes have been evaluated in a small cross-over human
intervention study with 7 healthy adults. Plasma total antioxidant power and the effect on
lymphocyte DNA damage and repair were assessed before and after each treatment of a single
dose (3.3 g) of G. lucidum or water (control). G. lucidum caused an acute increase in plasma

52

particularly glucans.11 Hepatitis Clinical effects and safety evaluation of Agaricus Blazei Condensed Liquid (Agaricus Mushroom Extract.1. Glucan extracts from the Trametes versicolor mushroom have been shown to improve survival and immune function in human randomised clinical trials of cancer patients. GI tract and spleen. However. terpenes and furans have also been implicated in immune function. although clinical proof is lacking. 5. A systematic review of human clinical trials has concluded that numerous dietary polysaccharides.3-β-glucans. Glucans. Structure-function relationships of betaglucans are of particular importance in their immunomodulatory effects (Thompson et al.. 2010). While considerable in vitro data exists. mushroom proteins. thought to inhibit tumor growth by stimulating the immune system via effects on NK cells.. Treatment with Ganopoly® for 12 weeks showed hypoglycemic activity and produced some anti-viral and liver protective effects in patients with chronic hepatitis B infection. arabinogalactans and fucoidans elicited immunomodulatory effects in controlled studies of 53 . the findings suggest that Ganopoly® may have some pharmacological activities. the same treatment regimen did not result in any objective response in late-stage cancer patients (Zhou et al. chronic hepatitis B. More recent work has implicated polysaccharides with varying sugars and some are α.rather than β-glucans. lucidum have no effect on DNA resistance to oxidative stress or repair in vivo (Wachtel-Galor et al. 5. appear to elicit diverse immunomodulatory effects in animal tissues.12 Immune Function Numerous studies have described the effects of mushrooms and mushroom extracts on immune function with implications for inhibiting tumor growth. ABCL) administered to human volunteers (10 male. macrophages and via T cells and their cytokine production. 2010). coronary heart disease. 2005).1..6-branched 1. including the blood. in vivo studies are few and the limited clinical studies that have been carried out have been with small numbers of patients and have often been poorly controlled. A series of trials have evaluated Ganoderma lucidum on cancer. Some of the more efficacious compounds reported are the 1. Overall. 2002). 10 female) with chronic C-type hepatitis orally twice per day for 8 weeks reported no toxicological or other side effects (Inuzuka and Yoshida.antioxidant power. and neurasthenia. but did not significantly affect the level or rate of repair in lymphocytic DNA suggesting that the bioavailable antioxidants absorbed from G. Type II diabetes. Furthermore.

Danshen (Salvia miltiorrhiza)) showed significantly elevated B-lymphocytes in patients with breast cancer after taking YunzhiDanshen capsules. At the end of the supplementation period.P leuran significantly reduced the incidence of URTI symptoms and increased the number of circulating NK cells. The mechanisms of pleuran function are yet to be determined (Bergendiova et al. on selected cellular immune responses and incidence of URTI symptoms in athletes. an insoluble beta-(1. the athletes underwent a 20 min intensive 54 ... no changes from baseline were detectable for any parameter in either the placebo (n=29) or the mushroom (n=28) group (Lima et al. respectively. once per day for 2 months. 2009). placebo-controlled trial has evaluated the effects of Agaricus blazei Murrill intake (900 mg/day for 60 days) on serum levels of interleukin-6 (IL-6). 2012). The dose-response curves for many endpoints were non-monotonic with intermediate doses having either immune enhancing or immune suppressing effects in peripheral blood compared with both high and low doses (Deng et al.. In addition. taking pleuran or placebo supplements during 3 months. Incidence of URTI symptoms together with characterization of changes in phagocytosis and natural killer (NK) cell count was monitored. This systematic review provides a high level of evidence for these effects (Ramberg et al.healthy adults and patients with canker sores and seasonal allergies. A randomized.6) glucan from mushroom Pleurotus ostreatus.. In a similar double-blind pilot study. these groups consumed 100 mg of beta-glucan (Imunoglukan) or placebo supplements. A double blind. 2011). the phagocytosis process remained stable in pleuran group during the study in contrast to placebo group where significant reduction of phagocytosis was observed. 2010).3/1. A polysaccharide extract from Grifola frondosa (Maitake extract) has shown immunomodulatory effects in a phase I/II dose escalation trial in post-menopausal breast cancer patients (n=34). No dose-limiting toxicity was encountered and there was a statistically significant association between Maitake and immunologic function. placebo-controlled study has investigated the effect of pleuran. After 60 days. These findings indicate that pleuran may serve as an effective nutritional supplement for athletes under heavy physical training. double-blind. 2005). Another clinical trial in breast cancer patients (n=82) evaluating the immunomodulatory effects of Yunzhi-Danshen capsules (Yunzhi (Coriolus versicolor).. while plasma sIL-2R concentration was significantly decreased (Wong et al. interferongamma (IFN-gamma) and tumour necrosis factor-alpha (TNF-alpha) in 57 community-living elderly women. Fifty athletes were randomized to pleuran or placebo. 20 elite athletes were randomized to beta-glucan (n=9) or placebo ( n=11). Prolonged and exhausting physical activity causes numerous changes in immunity and sometimes transient increases the risk of upper respiratory tract infections (URTIs).

ranging from two to 399-fold (TNFα). After stimulation of whole blood from healthy volunteers ex vivo with 0. whereas no significant reduction in NK cell activity was found in the beta-glucan group. a significant reduction was observed in levels of IL-1-β (97%).0% of a mushroom extract. a dose-dependent increase in all the cytokines studied was seen. IL-17 (50%) and IL-2 (46%). Discrepancies in results have been reported between ex-vivo and in vivo studies. While 55 .. These results indicate that insoluble beta-glucan supplementation from P. 2009a) but a retrospectively study by the same group has also evaluated the immunoregulatory effect of a dry powder preparation of Cordyceps sinensis mycelia on humans after renal transplantation (Ding et al.5-5. 2010). The synergistic effects of Cordyceps sinensis with the drug cyclosporine A in preventing allograft rejection was recently reported in rats (Ding et al. taking at least 30 days to obtain such an effect.. A 28% reduction in natural killer (NK) cell activity below baseline was observed in the placebo group during the recovery period (1 h after exercise). However. The discrepancy in cytokine release ex vivo and in vivo may partly be explained by the antioxidant activity of AbM in vivo and limited absorption of its large β-glucans across the intestinal mucosa to the reticuloendothelial system and blood.. ostreatus may play a role in modulating exercise-induced changes in NK cell activity in intensively training athletes (Bobovcak et al.exercise session. mainly containing Agaricus blazei Murill (AbM). in vivo. Immune cell counts did not differ significantly between the groups. AHCC also promotes T helper (Th) 17 and 1 cell responses via inducing IL-1beta production from monocytes in humans (Lee et al. 2010). Another nine cytokines remained unaltered (Johnson et al. 2009). alpha-glucans had lost their efficacy to stimulate the immune response as observed in an in vitro mouse model (Volman et al.. In healthy adults over 50 years of age. 2010b). TNF-α (84%). The authors suggested that in vivo. whereas no effect on IL-1β and IL-6 was observed. with the effect continuing up to 30 days after discontinuing treatment with AHCC (Yin et al... in eight volunteers who completed the daily intake (60 ml) of the AbM extract for 12 days. 2009b). 2012).. active hexose correlated compound (AHCC) enhanced CD4(+) and CD8(+) T cell immune responses. A double-blind randomized trial undertaken in mildly hypercholesterolemic subjects (n=56) to examine the effects of α-glucans from Agaricus bisporus reported that consumption of A. and no significant decrease in NK cell count was measured in the beta-glucan group during the recovery period. bisporus α-glucans lowered lipopolysaccharide-induced TNFα production by 69% compared to the control group.

and other blood chemistry) were not influenced by Lentinex (R). and the number. stimulate hemopoietic function. 2011) where two groups were given either 2. complement proteins and cytokines measured were not altered. 2010). as well as reduce the incidence of infection and the dosage of the drugs cyclosporine A and tacrolimus used. 2011). in 42 healthy. 2011). treatment did effectively protect liver and kidney. The immunoglobulins. The changes in the number of B-cells were significantly different between the groups. and therefore. elderly subjects has recently been evaluated in a double blind. and severity of adverse events were similar to placebo. suggesting anti-inflammatory effects (Forland et al. kidney function. then after a washout period of 4 weeks. chemotactic and some Th1-type cytokines (Forland et al. liver function. improve hypoproteinemia. Lentinex (R).. but there was no significant difference between the groups. Lentinex given orally to elderly subjects was deemed to be safe and induced an increase in the number of circulating B-cells (Gaullier et al.. n=11) in which baseline concentrations for the (17) cytokines ebaluated in the UC and CD patient groups were largely similar. n=10) and Crohn's disease (CD. The effect and safety of a soluble beta-glucan from Lentinus edodes mycelium. placebocontrolled trial (Gaullier et al. crossover. nature. but the AbM-based extract resulted in increased production of proinflammatory. pointing to an anti-inflammatory effect. Ingestion of an AbM-based medicinal mushroom by patients with IBD resulted in decreased levels of pathogenic cytokines in blood and calprotectin in faeces. Faecal calprotectin (a marker for inflammatory bowel disease (IBD) was reduced in the UC group. although an in vitro study by the same authors with monocyte-derived dendritic cells showed that AbM did not induce increased synthesis of Th2 or anti-inflammatory cytokines or the Th1 cytokine IL-12.there was no significant difference in graft survival rate or occurrence of reject reaction. The number of NK cells increased significantly in both groups... A randomised trial of 24 healthy volunteers has shown that consumption of 100 g of blanched Agaricus bisporus daily with a normal diet for 1 wk significantly accelerated 56 . This extract also modulated cytokines in patients with ulcerative colitis (UC.5 mg/day Lentinex (R) orally or placebo for 6 weeks. the alternate supplementation was given for 6 weeks. The safety blood variables (differential cell count. it may be useful for immunoregulation after organ transplantation. The mechanisms for such effects are unclear. An extract (AndoSan) from Agaricus blazei Murill (AbM) has been shown to reduce blood cytokine levels in healthy volunteers after 12 days of ingestion. Secretory immunoglobulin A (sIgA) acts as the first line of adaptive humoral immune defence at mucosal surfaces.

Many of the potential therapeutic effects of mushrooms and mushroom components on a variety of diseases appear to be directly or indirectly mediated by enhancing natural immunity of the host via effects on natural killer (NK) cells.. 2010b). macrophages. 2011).7% (30/72) and 69. Seventy-two patients were randomly assigned to receive Maitake extract (SXfraction: MSX) or clomiphene citrate (CC) monotherapy for up to 12 weeks. The ovulation rates for MSX and CC were: 76.. Lin et al. In the combination therapy.5% (29/31).9% (20/26) and 93. 2010).. and 41. A recent systematic review of immunomodulatory dietary polysaccharides concluded that glucan extracts from Trametes Versicolor improved survival and immune function in human randomised controlled trials of cancer patients (Ramberg et al.. 2011. 57 . The data suggest that the Maitake extract described in this study may induce ovulation in patients with polycystic ovary syndrome and may be useful as an adjunct therapy for patients who failed first-line treatment with clomiphene citrate (Chen et al. by the cycles.. Lima et al. respectively. 2009. 7 of 7 patients who failed in MSX monotherapy and 6 of 8 patients who failed in CC monotherapy showed ovulation. 2010b). Eighteen patients who did not respond to MSX or CC were subjected to combination therapy of MSX and CC for up to 16 weeks. Rondanelli et al..sIgA secretion. A mini-review on how the immunomodulatory actions of mushroom polysaccharides impact tumor cells has also been published (Wong et al. A recent study has also suggested that branching of the β-glucan chain is a requirement for immunostimulatory activity (Volman et al. 2009b).. 2011). Twenty-six patients in the MSX group and 31 in the CC group were evaluated for ovulation..9% (58/83). Reviews have been carried out on the immunobiology of mushrooms (Borchers et al. via balance of T cells and their cytokine production.. 2009). on the immunomodulatory activities of mushroom polysaccharides (Cheung et al. 5. Eight patients with documented history of failure to CC received combination therapy from the beginning. 2007a. thereby indicating its effect on the improvement of mucosal immunity (Jeong et al. respectively by the patients (NS).. The immunomodulatory effects of Agaricus blazei Murill and resultant impacts on an array of health outcomes have recently been reviewed (Hetland et al.13 Reproductive Health An open trial with 80 patients with polycystic ovary syndrome at three clinics in Japan has been undertaken. 2008). 2011).. 2011).1. and on the health effects of beta-glucans in mushrooms (Rop et al. and via the activation of Mitogen Activated Protein Kinase (MAPK) pathways (Kim et al..

This mechanism has been proposed in in vitro and animal trials. and a subsequent reduction in estrogen. the growing amount of data from human clinical trials suggest that the mushrooms and mushroom extracts tested are safe and generally well-tolerated.1. data showing protective effects of mushrooms on beta-amyloid peptide toxicity in the brain and mild cognitive impairment (both precursors to dementia and Alzheimer’s Disease) are very exciting and warrant further research. and more recently in a human trial of postmenopausal women diagnosed with breast cancer. affecting estrogen receptor positive tumors may provide a mechanism for these effects of mushrooms in breast cancer treatment. recent studies have suggested that an inhibition of aromatase activity. although the majority of data are based on food frequency /diet recalls.14 Summary of Human Studies In general. However. 58 .5. The most promising data appear to be those indicating an inverse relationship between mushroom consumption and breast cancer risk. Recent evidence has also suggested that the anti-aromatase compound is conjugated linoleic acid (CLA). Although preliminary.

2008) and insulin sensitivity possibly via regulation of lipid metabolism (Cho et al..3g/kg) lowered the serum glucose level in obese/diabetic (+db/+db) mice after one week of treatment through the suppression of hepatic PEPCK gene expression (Seto et al.. the same result was not observed with Ganoderma lucidum and Grifola frondosa.03 and 0. Kim et al. The hypoglycemic potential of EPS was also confirmed by histopathological examination that showed that EPS administration is able to restore impaired kidneys to almost normal architecture (Hye-Jin et al. 2009) on an adrenaline-induced increase in blood glucose in mice. 2007) in diabetic mouse models. total cholesterol and triglyceride. Intake of Pleurotus eryngii also significantly reduced the homeostasis model measurement of insulin resistance. 2008) in streptozotocin-induced rats. 2009)... A similar anti-hyperglycemic effect has been reported by Grifola frondosa (Cui et al. and increased high density lipoprotein (HDL)-cholesterol levels demonstrating hypoglycaemic and hypolipidemic effects and an improvement in insulin sensitivity in this mouse model (Jung-In et al. A polysaccharide isolated from Phellinus linteus reportedly inhibited the development of autoimmune diabetes by regulating cytokine expression in non-obese diabetic mice (Kim et al. Aqueous extracts of Pleurotus pulmonarius also have been shown to possess hypoglycemic activity (Badole et al..1 Animal model (mouse) studies Aqueous extracts of various mushrooms have been shown to possess hypoglycemic activity and anti-hyperglycemic activity against diabetes-inducing compounds in obese and diabetic animal models. 2010. 2009) and Coprinus comatus (Han and Liu. 2010d). A hypolipidemic effect of Pleurotus eryngii extract 59 . Extracellular polysaccharides (EPS) from Laetiporus sulphureus var. 2010c). although in this study.. 2007) in alloxan-induced diabetic mice... Intake of Pleurotus eryngii (5% supplementation with a normal diet) has been shown to decrease plasma glycated haemoglobin and serum glucose levels in a diabetic (db/db) mouse model. An aqueous extract of Ganoderma lucidum (0.. as well as having synergistic antihyperglycemic effects with acarbose (Badole and Bodhankar. Anti-diabetogenic Properties 6. 2006). miniatus have been shown to both stimulate insulin secretion (Hwang et al. 2007) as well as pancreatic islets of Langerhans (Yamac et al.6..

. Compared to the water administered control group.. The structure and anti-tumour activity of polysaccharide fractions of the fruit body of Agaricus brasiliensis have been studied in cold and hot water extracts (CWE and HWE) on a mouse diabetic model (C57BL Ksj-db/db). Polysaccharides extracted from Inonotus obliquus (Pers. 2/5 (HWE). level of fasting plasma glucose. antilipidperoxidative.. triglycerides. Moreover. Treatment with MT-alpha-glucan significantly decreased the body weight. cholesterol. free fatty acid and malondialdehyde content in liver. the insulin binding capacity to liver crude plasma membranes increased and histopathological changes in the pancreas were ameliorated in the treatment group. 2010).: Fr. reduced glutathione and the activity of liver superoxide dismutase and glutathione peroxidase. which may be related to its effect on insulin receptors by increasing insulin sensitivity and ameliorating insulin resistance of peripheral target tissues (Lei et al.has also been shown in fat-loaded mice and suggested to be due to low absorption of fat caused by the inhibition of pancreatic lipase (Mizutani et al. the number of the mice having abnormal kidney was 3/5 (control). 2007).. serum insulin. The splenocytes of CWE administered mice produced a higher concentration of interleukin-6.) Pilat (Aphyllophoromycetideae) have also been shown to have antihyperglycemic. 2011). 2006). A hypolipidemic effect of Ganoderma lucidum (Leyss:Fr) Karst has also been demonstrated in a mouse model (Rubel et al. The data suggested that MT-alpha-glucan has an anti-diabetic effect on KK-Ay mice. and antioxidant effects in alloxan-induced diabetic mice (Xu et al. 60 .. the body weight. The results suggested that the pharmacological action of the cold water extract of A. 2010). urinary pH. brasiliensis is significantly stronger than that of the hot water extract (Furukawa et al. and 0/5 (CWE) suggested the activity of the renal protection in the cold water extract. urinary glucose exclusion. glycosylated serum protein. and organs weight were comparable. blood glucose level. Treatment with MT-alpha-glucan significantly increased the content of hepatic glycogen. The anti-diabetic effect of an alpha-glucan (MT-alpha-glucan) from the fruit body of Maitake mushrooms (Grifola frondosa) on KK-Ay mice (a type 2 diabetes animal model) has been evaluated. By megascopic and microscopic examinations of renal sections.

. 2011). and antiarteriosclerotic activity indicating overall anti-diabetic activity in diabetic rats. followed by a reduction in the A. Treatment with mushroom Pleurotus ostreatus extract has been suggested to reduce high blood glucose level. an inhibitor of the non-enzymatic glycosylation (NEG) reaction. Comatin. A hypoglycemic effect on streptozotocin-induced diabetic rats has also been demonstrated by Agaricus bisporus (Sang Chul et al. genetic alterations (DNA fragmentation. purified from Coprinus comatus fermentation broth and identified as 4.14 mM to 4. anti-hypercholesterolemic. The blood glucose concentration of normal rats treated by comatin at 80 mg/kg body weight was reduced from 5.. However.5-dihydroxy-2-methoxy-benzaldehyde.6. Pulmonary lipoperoxidation increased in the diabetic animals compared to the control group. Blazei-treated group. Semipurified fractions of a submerged-culture broth of Agaricus blazei Murill were also reported to reduce blood glucose levels in streptozotocin-induced diabetic rats (Oh et al. including mushrooms on hypoglycaemia in streptozotocin-induced diabetic rats has been evaluated (Sandeep et al. An aqueous extract of Agaricus blazei Muril administered daily starting 40 days after the onset of streptozotocin-induced diabetes in Wistar rats assisted in the recovery of pulmonary tissue of the rats. the enzymatically hydrolyzed oligosaccharides have been shown to have around twice the activity of β-glucans with respect to anti-diabetogenic activity (Kim et al.. administered at 400 mg/kg body weight per day for 7 days resulted in a 29. indicating that comatin could maintain a low level of blood glucose and improve glucose tolerance (Ding et al. 2010). The A. while the concentrations of fructosamine.2 Animal model (rat) studies Beta-glucans and their enzymatically hydrolyzed oligosaccharides from Agaricus blazei have anti-hyperglycemic. 2010) and by polysaccharides from Laetiporus sulphureus (Hwang and Yun. Blazei treatment effectively reduced the oxidative stress and contributed to tissue recovery (Di Naso et al. triglycerides and total cholesterol in alloxan-induced diabetic rats were significantly decreased... Furthermore.. 2010). 2010). anti-hypertriglyceridemic. Blazei-treated group. chromosome aberrations) and sperm abnormalities in streptozotocin-induced diabetic rats (Ghaly et al. iNOS was increased in the lung in diabetic rats and reduced in the A. 2010). The pulmonary tissue in diabetic rats showed oxidative alterations related to the streptozotocin treatment. The characterisation and efficacy of beta-glucans from different sources. 2005). 2011). a hot water extract of Agaricus bisporus.28 mM in 3 h..68% 61 .

The decreases in total cholesterol. Agaricus bisporus has been shown to lower blood glucose and cholesterol levels in streptozotocin (STZ)-induced diabetic and rats fed a hypercholesterolemic diet (Jeong et al. the hypothesis remains to be proven. respectively). and being able to attenuate a diabetes-induced increase in blood glucose concentrations (Guo et al.1%.. whereas stimulation of fat cell glucose oxidation was a general property of the lectins. In hypercholesterolemic rats.reduction of serum glucose levels. A similar significant decrease in hepatic cholesterol and triglyceride concentrations was observed (36.8%. low-density lipoprotein.. However.7%.2% and 20. None of nine other lectins tested stimulated insulin release.. respectively).8% and 33. 2011). sinensis having an antidepressantlike activity. The authors proposed that the specific interaction between mushroom lectin and its receptors may lead to conformational changes in the 62 . The lectin did not alter islet glucose oxidation to CO2 or incorporation of [3H] leucine into trichloracetic acid-precipitable material. 2010). Maximal stimulation of insulin release was reported at lectin concentrations above 58 µg/mL (approximately 1 µM). liver enzyme activities. a most interesting effect of the treatment was the increase in cellularity of the Langerhans islets of the pancreas and their apparent repopulation with beta cells (Yamac et al. respectively). However. with serum insulin levels significantly increasing in streptozotocin-induced diabetic rats.7% and 15. has been hypothesized as a possible treatment approach to both diabetes and depression. nor did it modify rates of insulin secretion induced by 20 mM glucose. and liver weight gain. oral feeding of the Agaricus bisporus powder for 4 weeks resulted in a significant decrease in plasma total cholesterol and low-density lipoprotein (22. The STZ-induced diabetic male Sprague-Dawley rats fed Agaricus bisporus powder (200 mg/kg of body weight) for 3 weeks had significantly reduced plasma glucose and triglyceride concentrations (24. Lectins from Agaricus bisporus and Agaricus campestris have been shown to stimulate insulin and glucagon release from isolated rat islets in the presence of 2 mM glucose. 2010. Vanadium-enriched Cordyceps sinensis (VECS).. The data also suggested that lectin binding is essential for the expression of insulin-releasing activity. based on vanadium compounds having an ability to imitate the action of insulin and C.1%. and triglyceride concentrations were accompanied by a significant increase in plasma high-density lipoprotein concentrations demonstrating significant hypoglycemic and hypolipidemic activity in rats. respectively). Guo et al. alanine aminotransferase and aspartate aminotransferase (11. 2010).7% and 39.

and increased plasma insulin by 22. The hypoglycaemic effect of exo-polymers (EPs) produced from submerged mycelial cultures of several varieties of mushrooms on streptozotocin (STZ)-induced diabetic rats have been investigated. A subsequent study by the same group. The results demonstrate the potential of HE exo-polymer in treating hyperlipidemia in dietary-induced hyperlipidemic rats (Yang et al. and liver total cholesterol (28..6%).5%. however.. 2002a).5%. Phellinus pini (PP).9%).1% compared to the control group.1 and 44. Plasma glucose and total cholesterol were also reduced by administration of Phellinus linteus EPs. respectively (Yang et al.. The animals were administered with exo-polymers at the level of 100mg/kg body weight daily for four weeks. and triglyceride levels were observed in rats fed with Lentinus edodes and Cordyceps militaris EPs..0%).7%). compared to the saline administered (control) group. 1975). A hypolipidemic effect was achieved in all the experimental groups. 2004). 2001).structure of the membranes of the islet A2. using higher concentrations (200mg/kg body weight in streptozotocin-induced diabetic rats) of exo-polymers from a submerged mycelial culture of Lentinus edodes has shown that the administration of the exo-polymer reduced the plasma glucose level by as much as 21. but the triglyceride level was not changed significantly. Similarly. low-density lipoprotein (LDL) cholesterol (39.and B-cells that facilitate exocytosis (Ewart et al. The five experimental groups were fed with EPs (50mg/kg body weight) for 7 days.. The result demonstrates the hypoglycaemic activity of EPs of three mushroom varieties in STZ-induced diabetic rats and suggests some potential in the control of diabetes mellitus (Kim et al. significantly reducing plasma triglyceride (28. Flammulina velutipes (FV). and Grifola frondosa (GF) has been investigated in dietary-induced hyperlipidemic rats. HE exo-polymer proved to be the most potent.and endo-biopolymers produced by a submerged mycelial culture of Ganoderma lucidum in streptozotocin-induced diabetic rats has also been reported (Yang et al. 63 . The EPs of the three mushroom species also demonstrated a marked reduction in the level of plasma glutamate-pyruvate transaminase (GPT). 2002c). a hypoglycaemic effect of exo. phospholipid (16. total cholesterol (29. Significant reductions in plasma glucose. It was also shown to lower the plasma total cholesterol and triglyceride levels by 25. Auricularia auricula judae (AA).9%) levels. The hypolipidemic effect of exo-polymers produced in submerged mycelial cultures of Hericium erinaceus (HE). total cholesterol.

while the presence of anti-hyperglycaemic. Water consumption in the FCM-fed OLETF rats tended to be less than in both the OLETF control and CM-fed OLETF rats. 2002).Oral administration of Maitake mushroom fractions has been shown to lower blood pressure and fasting blood glucose of Zucker fatty rats. alone or combined with other natural products such as bitter melon and niacin-bound chromium.. 2006). Water consumption was significantly higher in the OLETF control than the LETO rats.. Phellinus linteus. a model of insulin resistance and type 2 diabetes mellitus. and Paecilomyces tenuipes in 90% pancreatectomized rats has also been reported (Choi et al. Rats were fed a semi-synthetic diet supplemented with 50g/kg Chaga mushroom powder (CM) or 50g/kg fermented Chaga mushroom powder (FCM) for 8 weeks (26 to 34 weeks of age). The data suggested that orally ingested fermented Chaga mushroom has a possible beneficial effect on the complications known to occur in obesity-related non-insulin dependent diabetes mellitus (NIDDM) OLETF rat (Cha et al. insulin-releasing and insulin-like activity in Agaricus campestris in streptozotocin (STZ)induced diabetic mice has also been demonstrated (Gray and Flatt... Nondiabetic Long-Evans Tokushima Otsuka (LETO) rats were used as age-matched nondiabetic control animals. 2007). may be useful in the treatment of insulin resistance (Talpur et al. the consumption of FCM resulted in a significantly lower serum triglyceride concentration and slightly lowered serum total cholesterol concentration when compared to the OLETF control and CM-fed rats. The effects of fermented Chaga mushroom (Inonotus obliquus) powder on the lipid concentrations and the activities of liver marker enzymes of serum in genetically diabetic Otsuka Long-Evans Tokushima fatty (OLETF) rats have ben studied. The authors concluded that specific fractions of Maitake mushroom. The livers of the OLETF CM-fed rats showed less fatty changes compared to the OLETF control rats and fat deposition in the hepatocytes was nearly absent. 1998). 2004b). 64 . An improvement of insulin resistance and insulin secretion by water extracts of Cordyceps militaris. Serum concentrations of triglycerides and total cholesterol were significantly higher in the OLETF control rats than in the LETO rats while within the OLETF rat groups. Enhanced insulin-hypoglycaemic activity (improvement in insulin sensitivity) has also been reported in spontaneously hypertensive rats consuming a glycoprotein extracted from Maitake mushrooms (Preuss et al.

Ganoderma lucidum polysaccharides have also been shown to significantly and dose-dependently increase nonenzymic and enzymic antioxidants. superoxide radicals. 2008). (Family Polyporaceae) in STZ-induced diabetic rats.. The differential expression patterns of rat kidney proteins from normal. A histopathological examination showed that EPS administration restored the impaired kidney in STZ-induced rats to almost normal architecture (Hye-Jin et al. Intracellular reactive oxygen species scavenging activity of hispidin was approximately 55% at a concentration of 30 M. 2007). 2010a). STZ-induced diabetic. and EPS-treated diabetic rats. 65 . fructosamine.. Plasma insulin levels of STZ-induced diabetic rats decreased compared to control rats.. The hypoglycaemic potential of the EPS was further supported by histological observations of pancreatic islets of Langerhans (Yamac et al. 2007).1% at the dose of 150 mg/kg of body weight. were analysed.) Fr. hispidin was shown to inhibit hydrogen peroxideinduced apoptosis and increased insulin secretion in hydrogen peroxide-treated pancreatic beta-cells indicating that hispidin may have anti-diabetogenic properties via protection of pancreatic beta-cells from reactive oxygen species in diabetes (Jang et al. In addition.3 In vitro studies Hispidin from Phellinus linteus exhibited quenching effects against DPPH radicals. Following oral administration of exopolysaccharide produced from submerged mycelial culture of Lentinus strigosus (Schwein.A hypoglycaemic effect of extracellular fungal polysaccharides (EPS) in STZ-induced diabetic rats has been reported. Submerged-culture mycelia and broth of Grifola frondosa have been shown to contain bioactive components for improving glycaemic responses.. 2009). A similar study with Ganoderma lucidum has reported both hypoglycaemic and anti-hyperglycaemic effects in Wistar rats (Mohammed et al.. and blood glucose concentrations in male Wistar rats injected with nicotinamide plus STZ (diabetic rats) (Lo et al. serum insulin level and reduce lipid peroxidation and blood glucose levels in STZ-diabetic rats (Jia et al. such as decreases in serum triglyceride. their serum glucose levels were reduced by up to 21. and hydrogen peroxide in a dose-dependent manner. 2008). 6.

7. enhancement of antioxidant defence.1 Animal model studies Anti-bacterial effects of Agaricus blazei Murill (AbM) have been demonstrated with the AbM extract being protective against systemic Streptococcus pneumoniae 6B infection in mice. Bacterial 66 . 2005a. A subsequent study by the same group has shown that an extract of Agaricus blazei Murill can protect against lethal septicemia in a mouse model of faecal peritonitis. and regulation of insulin-dependent and insulin independent signalling pathways have recently been reviewed (Lo and Wasser. The efficacy of medicinal mushrooms (as a whole rather than for individual varieties) for glucose control in diabetes. have confirmed the hypoglycaemic effects of mushrooms and mushroom components. protection of beta-cell damage. The extract was most effective when given 24h before inoculation but it also had protective effects when given together with challenge compared with control. attenuation of inflammation. Bernardshaw et al. modulation of carbohydrate metabolism pathway. 2011).6. The anti-infection properties of AbM have been shown in vivo and the results suggest that AbM extract may be useful as an additional prophylactic and possibly therapeutic treatment against bacterial infections in humans (Bernardshaw et al. increase of insulin release. indicated that the protective effect of AbM was due to the involvement of the native immune system.4 Summary of Anti-Diabetogenic Properties A large number of animal studies. The lack of an antibiotic effect on pneumococci in vitro and increased levels of cytokines MIP-2 and TNF in the serum of mice receiving AbM extract.and beta-glucans) via a direct interaction with insulin receptors on target tissues... in both normal and diabetic animal models. The hypoglycaemic effects appear to be mediated via mushroom polysaccharides (possibly both alpha. 2005b). Anti-microbial Properties 7. although this mechanism remains to be confirmed. including the inhibition of glucose absorption.

C. most or all collections of only four species. 2008). 2006. yeasts and mycelial fungi. It has been suggested that such antimicrobial effects of mushroom extracts may be indirect.septicemia can occur during gastroenterological surgery. The state of septicemia. C. Staphylococcus aureus. 2008). ethanol. C. C. [ D. Mice that were orally treated with Agaricus blazei Murill extract before bacterial challenge showed significantly lower levels of septicemia and improved survival rates (Bernardshaw et al. C. C. sinapicolor. abnormis. clelandii. [ Dermocybe canaria] 2.. The putatively anti-infective immunomodulatory action of Agaricus blazei Murill (AbM) has been studied in an experimental peritonitis model in BALB/c mice. with a polysaccharide-rich fraction of Agaricus brasiliensis being shown to increase host resistance against some infectious agents through stimulation of the microbicidal activity of macrophages (Martins et al. Boletus (Boletaceae). austrovenetus. memoria-annae. The mice were orally given an extract of AbM or phosphate-buffered saline 1 day before the induction of peritonitis with various concentrations of faeces from the mice. Fomitopsis (Fomitopsidaceae). Hohenbuehelia (Pleurotaceae). namely C. as measured by the number of colony-forming units of bacteria in blood. Cantharellus (Cantharellaceae). C.. Soboleva et al. austroviolaceus.. 67 . Encouraging results were found for a number of macrofungi in the genera Agaricus (Agaricaceae). C.. 2009a). and Strobilomyces (Boletaceae) showing good growth inhibition of Gram positive. aureus. persplendidus. 2011). Hearst et al. C. vinosipes and forty seven collections of un-described Cortinarius species exhibiting IC 50 values of ≤0. including several foodborne pathogenic bacterial strains (Venturini et al.. 2009. 2006). C.09 mg/mL against S. In contrast. 7. austrosaginus. kula]. C. and the survival rate of the animals were compared between the groups. coelopus. C.. Amanita (Amanitaceae). Lentinus (Polyporaceae). Similar screening for antimicrobial activity has been undertaken in 117 collections of Australian macrofungi belonging to the mushroom genus Cortinarius with 13 species. archeri. namely Cortinarius ardesiacus.2 In vitro studies Numerous in vitro studies have clearly demonstrated activities against gram-positive and gram-negative bacteria. including dermatophytes and phytopathogens (Jagadish et al.. C. Australia have been evaluated using water. and hexane extracts of freeze dried fruiting bodies. Gram negative and Escherichia coli bacteria (Bala et al. Ramaria (Gomphaceae). Antibacterial activity of an array of Australian basidiomycetous macrofungi collected across Queensland.

with E. while Volvariella volvacea strain ATCC62890 showed significantly less antimicrobial activity. a well-known beta-glucan receptor. Staphylococcus aureus. Studies with an aqueous extract of Agaricus brasiliensis S. and eleven un-described Cortinarius collections exhibited similar effects against P. TNF-alpha production. triggered by beta-glucans.coli having the highest susceptibility to the mushroom mycelia (Ofodile et al. 2011b). C. kula]. A recent report has suggested that the presence of tannins and flavonoids may be responsible for the positive antibacterial activity and antifungal activity of mushrooms against human pathogens (Parameswari and Chinnaswamy.austroalbidus. Enterobacter aerogenes. 2006). Ethanol extracts of Agaricus bisporus have also been shown to have antibacterial activity against 68 .09 mg/mL) (Beattie et al.) failed to show any anti-microbial effects against Salmonella enterica serovar Typhimurium (Fantuzzi et al... Activity against the Gram-positive bacteria Staphylococcus aureus. nitric oxide (NO). versicolor could be used as a nutritional supplement that may be useful in the treatment of infectious disease (Jang et al. aeruginosa (IC 50≤0. but was reported to be a source of antioxidants (da Silva et al. (=Agaricus blazei Murrill sensu Heinem. The effects of beta-glucans from Coriolus versicolor on phagocytic activity. in macrophages has been evaluated. Klebsiella pneumoniae and Pseudomonas aeruginosa. and these molecules seem to act as secondary molecules that cause eventual phagocytosis by macrophages. C. The mycelial culture of Ganoderma lucidum has been shown to be highly active against human pathogenic bacteria Escherichia coli. methanol and xylene extracts of these mushrooms (Tambekar et al.. The findings suggest that C. Agaricus bisporus and Pleurotus sajor caju have been assayed in vitro for their antimicrobial activities using aqueous and organic solvent extracts. persplendidus. 2011). 2011) nor on immunomodulatory properties (Fantuzzi et al. It has been shown that Escherichia coli 390. Wasser et al. 2010).. Escherichia coli 739. [ D. elicited TNF-alpha and NO-iNOS/eNOS production. Pseudomonas aeruginosa and Klebsiella pneumoniae were most sensitive to aqueous. and signaling of dectin-1.. has been demonstrated in Volvariella volvacea strain R83.. Dectin-1 signaling.. 2010). ethanol. 2010b). 2011).

Bacillus spp. enokipodins C (1) and D (2). 1999).. Escherichia spp. Two cuparene-type sesquiterpenes.. while the water extract was heat-labile (Hirasawa et al. The substance responsible for the activity was heat-stable and was suggested to be lenthionine. have been isolated from culture medium of Flammulina velutipes (Enoki). Lentinamycin B was found to be the main component responsible for the anti-bacterial activity of the L. and Porphyromonas spp. Candida albicans and to stimulate the growth of E. 2009). Prevotella spp. The active compounds were detected by preparative thin layer chromatography.both gram positive and gram negative bacteria.. edodes combining marked anti-bacterial properties and high yields of water soluble polysaccharides were screened.. including dermatophytes and phytopathogens. Extracts from fermentation broth and mycelium of 15 strains of Lentinus edodes have been shown to be active against gram-positive and gram-negative bacteria. Actinomyces spp. coli M-17.. yeasts and mycelial fungi. The strains differed by the set of the organisms susceptible to the action of the extracts. were relatively resistant to these compounds. edodes strains (Soboleva et al.... as well as anticandidal activity against Candida albicans (Jagadish et al.. of oral origin. The anti-bacterial activity of chloroform extracts and ethylacetate extracts were relatively heat-stable. 2001). 2005). Lactobacillus spp. Three anti-bacterial compounds extracted by chloroform. Staphylococcus aureus and Bacillus megaterium. edodes) at a concentration of 5% from the volume of the nutrient medium was found to produce a pronounced anti-microbial effect with respect to Escherichia coli O-114. and Candida spp. ethylacetate or water from dried Shiitake mushrooms (Lentinus edodes) have been reported to possess efficient antibacterial activities against Streptococcus spp.. The action of the juice of Shiitake mushrooms (L. edodes juice (Kuznetsov et al. In contrast. 69 . along with enokipodins A (3) and B (4). Staphylococcus spp. Enterococcus faecalis. other general bacteria.. Two were identified with UV and mass spectrometry as lentinamycin B and erytadenine (lentinacin). Staphylococcus aureus. The anti-microbial activity of the culture fluid of Lentinus edodes mycelium grown in submerged liquid culture has been demonstrated against Streptococcus pyogenes. 2006).. Bifidobacteria and lactobacteria exhibited resistance to the action of L. an anti-bacterial and antifungal sulphur-containing compound (Hatvani. such as Enterococcus spp. Strains of L.

A polysaccharide-rich fraction of Agaricus brasiliensis has been evaluated for candidacidal activity. and C.All the metabolites showed anti-microbial activity against the fungus Cladosporium herbarum. Methanol.. Twenty-nine of the 48 species tested had anti-microbial activity.. including 50% of the yeast and mould species in the trial. Bacillus subtilis and Staphylococcus aureus (Ishikawa et al. 2001). and gram-positive bacteria. Podaxis pistillaris (Podaxales.. The results suggested that this extract can increase host resistance against some infectious agents through stimulating the microbicidal activity of macrophages (Martins et al. and Staphylococcus aureus) have been screened. ethyl acetate. Vibrio parahaemolyticus. whereas NO production was not affected. and aqueous extracts accounted for 92. In a culture medium of P. Listeria monocytogenes. This compared favourably with the results from both the positive control (Ciprofloxacin) and Oyster mushroom. Based on spectral data their identity was established as epicorazine A(1). three epidithiodiketopiperazines were identified by activity-guided isolation. 2008). and ethyl acetate extracts from edible wild and cultivated mushrooms against nine foodborne pathogenic bacterial strains (Escherichia coli O157:H7. Salmonella Enteritidis. and expression of mannose receptors by murine peritoneal macrophages. Proteus mirabilis. pistillaris. Bacillus subtilis. Basidiomycetes) was found to exhibit antibacterial activity against Staphylococcus aureus. Gram-positive bacteria were more sensitive than Gram-negative bacteria to fungal extracts. 2006). Aqueous extracts of Shiitake and Oyster mushrooms have been tested qualitatively against a panel of 29 bacterial and 10 fungal pathogens. The treatment increased fungicidal activity and it was associated with higher levels of H2O2. Podaxaceae.2%. Shiitake mushroom extract had extensive anti-microbial activity against 85% of the organisms tested.. methanol. perfringens was the most sensitive microorganism. pistillaris (Al-Fatimi et al. 2009b). The treatment enhanced mannose receptor expression by peritoneal macrophages. antibiotic F 3822). 70 . hexane.8% of the positive assays. whereas the hexane extracts accounted for only 7. in terms of the number of species inhibited by the activity of the metabolite(s) inherent to the Shiitake mushroom (Hearst et al. Serratia marcescens and Escherichia coli. Clostridium perfringens. epicorazine B(2) and epicorazine C (3. The anti-microbial activity of aqueous. Micrococcus flavus. which have not previously been reported as constituents of P. Bacillus cereus. Yersinia enterocolitica. H2O2 and nitric oxide (NO) production. Shigella sonnei.

2012).Aqueous extracts from Clitocybe geotropa and Lentinula edodes had the highest antimicrobial activity against the bacterial strains tested (Venturini et al. Antioxidant Properties A comparison has been undertaken of the antioxidant properties and phenolic profile of the most commonly consumed fresh cultivated mushrooms and their mycelia produced in vitro: Agaricus bisporus (white and brown). and Hericium erinaceus (17. edodes possessed the highest reducing power.6%). Pleurotus ostreatus (oyster). 2012). DPPH. 2012a). 7.. 8. A very small number of human studies have been completed.7%) also showed a relatively high Antioxidant Index (% relative to quercetin) (Abdullah et al. with in vitro. 2008). A small number of studies in animals have been undertaken and the data suggest that the anti-microbial effects in vivo may be mediated by effects of the immune system... determined by beta-carotene-linoleic acid. There was no correlation between the studied commercial mushrooms and the corresponding mycelia obtained in vitro (Reis et al.3 Summary of Anti-Microbial Properties Anti-microbial effects of a large number of mushroom varieties and mushroom components on both gram-positive and gram-negative bacteria have been confirmed via in vitro studies. L. in vivo samples revealed higher antioxidant properties than their mycelia obtained by in vitro techniques. and xanthine oxidase inhibitory activity have been 71 . Strong antioxidant properties have recently been described for a water-extractable polysaccharide fraction from Lentinus edodes (Shiitake) (Chen et al.1%). Generally. reducing power. Pleurotus eryngii (king oyster) and Lentinula edodes (shiitake). Schizophyllum commune (27.. Of the mushrooms evaluated. ferrous-ion chelating abilities. Antioxidant activity. the mushroom species with the highest antioxidant potential was Agaricus bispous (brown). while aqueous extracts of Ganoderma lucidum (30. but the antimicrobial effects of mushroom consumption remains to be confirmed in humans.

Antioxidant activity was measured using reducing power. The EC50 values (<20 mg/ml) indicate that the G. 2011a).and methanol-extracts from the fruiting bodies of Pleurotus eryngii (Alam et al.. acetone. 2011). 72 . Antioxidant properties and antioxidant compounds of various extracts from dried Grifola frondosa (Maitake) have been determined. Ergothionine has been shown to have anti-oxidative/antiinflammatory properties in several edible mushrooms (Ito et al. thereby potentially protecting against the occurrence of age-associated disorders that involve free radicals (Jayakumar et al. heart. 2011). Pleurotus eryngii and Auricularia auricula-judae both exhibit a protective effect against H2O2 induced oxidative cell damage with a P. frondosa extracts studied have potent antioxidative activity (Jan-Ying et al. 2010b). Phenols... eryngii methanolic extract also possessing the higher ferrous iron chelating ability (IC50 = 0.demonstrated in aqueous-. glutathione reductase (GR). The in vitro and in vivo antioxidant effects of the oyster mushroom Pleurotus ostreatus have recently been reviewed (Jayakumar et al.. The results suggest that this extract of P.. ostreatus can prevent the oxidation of GSH and protect its related enzymes during aging (Jayakumar et al. and glucose 6-phosphate dehydrogenase (G6PDH) in liver. ascorbic acid and alpha-tocopherol were found to be the major antioxidant components in the various mushroom extracts examined. flavonoids. 2011). velutipes with higher phenolics content showed more efficient antioxidant capacity against lipid oxidation. These results suggest that the inedible parts and spent culture medium of F. A further study by the same group also showed that administration of an extract of P.ostreatus to aged rats resulted in a significant increase in the levels of reduced glutathione (GSH) and elevated activities of glutathione S-transferase (GST). velutipes could potentially be considered as a readily available source of natural antioxidants (Bao et al. has been shown to increase gene expression of the antioxidant enzyme catalase and reduce the incidence of free radical-induced protein oxidation during aging in rats. kidney. The amount of ergothioneine was distributed highest in the inedible (base and mycelium) parts of the mushroom. An extract of Pleurotus ostreatus (200 mg/kg body weight).42 mg/ml) (Oke and Aslim. 2011).. whereas extracts prepared from the spent culture medium of F. Extracts prepared from the fruiting body of Flammulina velutipes with a high ergothioneine content exhibited a stronger delay of the autoxidation activity of oxymyoglobin. 2010a). DPPH and superoxide radical scavenging and ferrous ion chelation activity assays.. and brain tissues of rats. 2010).

non-tumour-bearing and tumour-bearing mice. 2008). 2008). including some cancers (Matsuzawa. 2006). Thelephora aurantiotincta. marmoreus fruit body could induce an antioxidant effect. and the increase of antioxidant activity in the plasma of tumour-bearing mice was an important mechanism in cancer prevention. 2007)... Thelephora ganbajun. which were determined as thiobarbituric acid reactive substances. Antioxidant activity via inhibition of lipid peroxidation has been described in several studies. 2007). 2007)(Ajith and Janardhanan. The extracts also inhibited lipid peroxidation (LPO) in a concentration-dependent manner.. Volvariella volvacea (Mathew et al.. The authors concluded that this effect of Ganoderma lucidum may protect the heart from superoxide induced damage (Wong et al. Oral administration of the fruit body of H.. It was also suggested that the mushroom might play a role in the decrease of lipid peroxides through antioxidant activity induction (Matsuzawa. 2004a) and others have been reported to have significant antioxidant activities..1-diphenyl-2picrylhyrazyl (DPPH). this result indicated that heart damage induced by ethanol showed a higher malonic dialdehyde level compared with heart homogenate treated with Ganoderma lucidum.. Furthermore. Pleurotus florida and Pleurotus pulmonaris (Ajith and Janardhanan. 2006) and irritable bowel disease (Najafzadeh et al. 2003). Ganoderma lucidum exhibited a dose-dependent antioxidative effect on lipid peroxidation and superoxide scavenging activity in mouse heart homogenate. 2009). These results showed that the intake of H. 2004). A hot water extract from Ganoderma lucidum has been shown to have an antioxidative effect against heart toxicity in mice. Boletopsis grisea (Liu et al. marmoreus exhibited potent anti-tumour or cancerpreventive effects and caused a significant decrease in lipid peroxide levels. Phellinus rimosus. The antioxidant effects of Hypsizygus marmoreus have been studied for peroxyl and alkoxyl radicals by ordinary. 73 . The study also reported anti-angiogenic activities of Phellinus linteus (Song et al. It has also been suggested that the antioxidant capacities of mushrooms may have a potentially protective effect against a variety of disease states. Of particular interest is that the antioxidant activity (free radical scavenging activity) along with total phenolic and flavonoid concentration of Agaricus bisporus appears to be similar before and after boiling (Jagadish et al. Ganoderma lucidum (Reishi). Ethanol extracts of the mushroom Phellinus linteus have been shown to have antioxidant activities comparable to vitamin C in scavenging the stable free radical 1.Agaricus bisporus (Savoie et al.

the highest AA were found in Agaricus nevoi. boiled and ethanolic extracts of 74 . 2004b). respectively. or coumarins (Habrant et al. flavonoids. In vitro evaluation of antioxidant activities of Auricularia auricular has shown significant inhibition of lipid peroxidation.7% and from 2. Antioxidant activities of ten natural p-terphenyl derivatives from the fruiting bodies of three edible mushrooms (Thelephora ganbajun.1%. The extract possessed significant 2. 2009). stilbenes. In vitro evaluation of antioxidant activities of Auricularia auricular has also shown significant inhibition of lipid peroxidation.2-diphenyl-1-picrylhydrazil (DPPH). Asatiani et al. and ethyl acetate were used for extraction. Omphalotus olearius. Three solvents ethanol.. G. 2004). boiled and ethanolic extracts were shown to significantly increase nitric oxide (NO) production over the control (Acharya et al. 2007b). comatus increased from 46... as well as potent hydroxyl radical scavenging activity when compared to catechin. lucidum increased antioxidant status in liver mitochondria of aged mice compared with the aged controls. Thelephora aurantiotincta. and Flammulina velutipes showed high antioxidant activities (AA) at 2mg/ml. and potent hydroxyl radical scavenging activity when compared with the drug catechin.. Water extracts from Coprinus comatus. and Auricularia auricula-judae extracts at a concentration of 2mg/ml. 2009). Antioxidant properties were studied from 28 submerged cultivated mycelium Basidiomycetes strains of 25 species.. The IC50 value of crude. when the concentration of the extract increased from 2mg/ml to 4-8mg/ml with the authors suggesting that the extracts could be suitable as antioxidative agents and bioproducts (Asatiani et al. while crude. Antioxidant activity of submerged cultured mycelium extracts of higher basidiomycetes mushrooms has recently been reported. Agaricus nevoi.6% to 82. The natural mushroom pigment Norbadione A and three other pulvinic acids have been shown to display very efficient antioxidant properties in comparison to catechols. water (culture liquid). 2007a. 2. When the ethanol extracts were tested. The AA of ethanol extracts from Agrocybe aegerita and C. Boletopsis grisea) from China have also been reported (Liu et al.A more recent study has examined the effects of an extract of Ganoderma lucidum for its free-radical scavenging property and for effects on liver mitochondrial antioxidant activity in aged BALB/c mice (50 and 250 mg/kg body weight for 15 days) (Cherian et al.4% to 62.. 2'-azinobis (3-ethylbenzothiazolin-6-sulphonic acid) (ABTS) radical scavenging activities and ferric reducing antioxidant power (FRAP) as well as superoxide and hydroxyl radical scavenging activities.

except for the extract of Lentinula edodes (Fui et al. 2002). The mycelia extracts however were more effective in the ABTS radical scavenging activity and ferrous ion chelating ability (Carvajal et al.1 Phenolic Content Determination of the phenolic and organic acid contents of Agaricus brasiliensis as well as the antioxidant activities of its fruiting bodies and its mycelia obtained from submerged cultivation has shown the presence of 3 phenolic compounds (gallic acid.. auricula represented 403. citric. syringic acid and pyrogallol) and 8 organic acids( benzoic. acetic. 2009). alpha-ketoglutaric. Ganoderma lucidum (Reishi). 2004). have also been shown to have a hepatoprotective effect on CCl4--induced liver injury in mice. Antioxidative activities of Flammulina velutipes extract have also been reported to be able to stabilize the fresh colour of tuna meat during ice storage (Bao et al. 572 and 398 µg/ml respectively of lipid peroxidation. The order of inhibitory activity of mushroom extracts on oxidation in an emulsion system was Agaricus bisporus > Hypsizigus marmoreus > Volvariella volvacea > Flammulina velutipes > Pleurotus eryngii > Pleurotus ostreatus > Hericium erinaceus > Lentinula edodes. 2007).A. suppressed 75 . using lard. 2012). The fruiting body extracts were more effective in the DPPH radical scavenging activity and lipid peroxidation inhibition than the mycelia extracts. 8. and 373 µg/ml respectively of hydroxyl radical scavenging activity and 310.. malic. Pleurotus florida and Pleurotus pulmonaris have also been reported to have significant antioxidant activities (Ajith and Janardhanan. Phellinus rimosus. while crude.. oxalic. The antioxidative potency of commercially available mushrooms in Taiwan has been studied. All extracts possessed antioxidant properties. The intravenous administration of syringic acid and vanillic acid significantly decreased the levels of the transaminases. In a thermal oxidative stability test. boiled and ethanolic extracts were shown to significantly increase nitric oxide production (664.. the order of antioxidative activity of the mushroom extracts showed similar tendencies. 191 and 850 pmole/mg dry wt/h respectively) over the control (Acharya et al. fumaric and trans-aconitic acids). 510. syringic acid and vanillic acid from Lentinula edodes mycelia that have radical scavenging activity. The phenolic compounds.

collagen accumulation and significantly decreased hepatic hydroxyproline content. young (YB) and mature (MB). The antioxidant activities of two edible mushrooms (Lentinus edodes and Volvariella volvacea) against lipid peroxidation have been shown to correlate with the phenolic content in different sub-fractions of the mushroom extracts (Cheung and Cheung. 2005).. Agrocybe cylindracea. respectively (Choi et al. significant correlation was found between the total phenolic content from the fruiting bodies of Agrocybe aegerite and antioxidant activity in an ethyl acetate fraction and its sub-fractions (Lo and Cheung. 2004)... but with similar antioxidant activities. The free polyphenolic content in the extract heated at 121ºC for 30min was increased by 1. The 2. have been evaluated with minor differences in the composition of phenolic compounds being detected. Similarly. 2010). Syringic and vanillic acid may therefore play a role in the suppression of hepatic fibrosis in chronic liver injury (Itoh et al.0-fold and 2. except for the chelating ability for ferrous ions. Extracts of Agaricus blazei. and 1..81mg/g) (Tsai et al.. Both of these compounds inhibited the activation of cultured hepatic stellate cells. which was higher in MB than in YB (Soares et al. Thermostable antioxidant activity has also been reported from Agaricus blazei Murill (Izawa and Inoue.18mg/g) and total phenols (5. and maintained hepatocyte viability. 2009). Heat treatment of Shiitake (Lentinus edodes) significantly increases its antioxidant activity and polyphenolic compounds.1-diphenyl-2picrythydrazyl (DPPH) radical scavenging activities were increased by 2. 76 . 2006a). 2008).1-distyrylpyrylethan. hypholomine B. The antioxidant capacity and total phenolic content of Agaricus brasiliensis in two stages of maturity.2fold compared to the raw sample.2-azino-bis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical and 1. These compounds exhibit potent free radical scavenging activity (Jung et al.9-fold compared to that in the extract from the raw sample. which is the quantitative marker of fibrosis.67-5. The polyphenolic content and antioxidant activities in extracts has been shown to increase as heating temperature and time increased (100 and 121ºC for 15 or 30min). which play a central role in liver fibrogenesis. Antioxidant polyphenols from the mycelial culture of the medicinal fungi Inonotus Xeranticus and Phellinus Linteus have been isolated and identified as hispidin and its dimers. and Boletus edulis have been shown to have significant antioxidant properties with the naturally occurring antioxidant components including total tocopherols (3. 3. 2005). 2007).14'-bihispidinyl.18-6.

Total phenols have been shown to be the major antioxidant components in ethanolic extracts in a variety of culinary and medicinal mushrooms (Tsai et al. β-hydroxyergothioneine has been isolated from the mushroom Lyophyllum connatum. An ergothioneine derivative. In humans.N'-dimethylurea. Pleurotus ostreatus. Grifola frondosa) all contained a statistically significant greater amount of ergothioneine compared to A. 2006). Ergothioneine. bisporus.. with highest concentrations detected in specialty mushrooms. Tsai et al. and 77 . and oat bran..2 Ergothioneine Ergothioneine is a native membrane-impermeable thiol compound that is specifically accumulated in cells via the organic cation transporter OCTN1. Supplementation with L-ergothioneine has been shown to have a protective effect on the organs of rats against lipid peroxidation and to conserve the consumption of endogenous glutathione and alpha-tocopherol (Deiana et al. The antioxidant properties in mushrooms decrease significantly with storage time. eryngii. P. cysteine. 2009). 2004).. OCTN1 and ergothioneine have been implicated in the etiopathogenesis of autoimmune disorders. no significant difference was found between the specialty mushrooms studied (Dubost et al. bisporus studied. The ergothioneine content of mushrooms has been reported to be in the range of 0. 2007). Few foods contain ergothioneine. liver. The specialty mushrooms tested (Lentinus edodes. L-ergothioneine is a biologically active antioxidant produced by certain fungal species and mycobacterium.. kidney.0mg/g (dry weight). White Agaricus bisporus contained the least ergothioneine and portabellas (brown) contained the highest within the varieties of A.N-hydroxy-N'. and methionine. 2008. DPPH (1. The precursors to the synthesis of L-ergothioneine are the amino acids histidine. 8. Ergothioneine has been reported to exhibit cell protection only against copper(II)-induced toxicity but is far less potent than glutathione. 2008). indicting that ergothioneine is not involved in the intracellular antioxidant thiol defence system (Ey et al. with recommendations being made that mushrooms be stored at 4ºC for up to 6 days (Tsai et al.1-diphenyl-2-picrylhydrazyl) activities have also been shown to significantly correlate with total content of phenolic compounds in a variety of edible and medicinal mushrooms (Kim et al. black and red beans.. 2008).42... however.

Furthermore.connatin (N-hydroxy-N'.1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging assay. Protein supplement treatments during mushroom growth do not have a significant effect on the amount of L-ergothioneine produced by mushrooms. β-Hydroxyergothioneine showed the greatest protective activity against carbon tetrachloride-induced injury in primary culture hepatocytes (Kimura et al. All the compounds displayed the ability to scavenge free radicals..3mg/g dry weight in later flushes by several stress factors placed on the mycelia. edodes possessed the highest reducing power.3 Summary of Anti-Oxidant Properties A recent (2012) comparison of the antioxidant properties and phenolic profile of the most commonly consumed fresh cultivated mushrooms and their mycelia produced in vitro: Agaricus bisporus (white and brown). 2005).. 8. 2007). The antioxidant activities appear to be related to the polyphenolic content. indicating that Lergothioneine may be a stress factor. such as dry compost. Pleurotus eryngii (king oyster) and Lentinula edodes (shiitake) have reported that Agaricus bispous (brown)had the highest antioxidant potential in vitro. The radical scavenging activity of β hydroxyergothioneine was very similar to that of ergothioneine. Significant antioxidant activities in vitro have been reported in several varieties of mushrooms. A postharvest shelf-life study has also demonstrated that L-ergothioneine significantly decreased during postharvest storage for up to 6 days at 12ºC (Dubost et al. with one study reporting antioxidant capacity compable to vitamin C. Pleurotus ostreatus (oyster). 78 . Ergothioneine has been shown to have anti-oxidative/anti-inflammatory properties in several edible mushrooms. while L. L-ergothioneine was increased by up to 1. but the addition of histidine to compost has been reported to significantly increase the amount of L-ergothioneine. L-ergothioneine is a biologically active antioxidant and its production in mushrooms can be enhanced by addition of histidine to the growth medium/compost. based on a 1.N'-dimethylcitrulline) were also isolated.

with both compounds docking with the HIV-1 protease crystal structure. A farnesyl hydroquinone. ganomycin I. Lectins from Agaricus bisporus.. 2000). 2008).. Extracts from Phellinus linteus also provided protection against variant H5N1 influenza viruses (Ichinohe et al..9. which could be enhanced by succinylation (Wang and Ng.0 µg/mL.. The evidence for an anti-viral effect of several mushroom extracts via inhibition of HIV-1 reverse transcriptase and protease appears strong. Incubation of peripheral blood cells PBCs and hepatoma HepG2 cells with a laccase purified from oyster mushroom (Pleurotus ostreatus) which were then infected with 79 . Ganomycin B competitively inhibited the active site of the enzyme. Anti-viral Properties Extracts of Grifola frondosa (Maitake) have shown activity against hepatitis B virus (Gu et al. 2006). herpes simplex virus type 1 (HSV-1) replication in vitro (Gu et al. 2009).. while nebrodeolysin from Pleurotus nebrodensis has been shown to possess anti-HIV-1 activity in vitro (Lv et al. Anti-viral activity of several mushroom extracts has been demonstated in vitro and in vivo in animal models. 2009). 2009). respectively (El Dine et al.. 2006).5 and 1.. 2001). A polysaccharopeptide from the Turkey Tail mushroom Trametes (=Coriolus) versicolor was reported to inhibite HIV-1 reverse transcriptase and protease. A ubiquitin-like protein from Pleurotus ostreatus has also demonstrated inhibitory activity toward HIV-1 reverse transcriptase. Momordica charantia. Phaseolus vulgaris. PR8) infection were shown to be dose dependent with low-dose AHCC supplementation improving the response to influenza infection despite no effect on total NK cell cytotoxicity (Nogusa et al. isolated along with ganomycin B. 2009). The effects of a mushroom-derived active hexose correlated compound (AHCC) on the immune response to influenza A virus (H1N1. from Ganoderma colossum has been reported to inhibit HIV-1 protease with IC50 values of 7. 2010).. 2008) and from Ganoderma sinense (Sato et al. Ricinus communis and its constituent chains have been shown to inhibit HIV-1 reverse transcriptase (Wang and Ng.. 2007) and against the growth of influenza A/Aichi/2/68 virus (Obi et al. the two enzymes of paramount importance to the life cycle of the HIV (Tzi et al.. Anti-HIV-1 protease activity was also reported for lanostane triterpenes from Ganoderma colossum (El Dine et al.

2010b). 2010).5 mg/ml after the first dose of treatment for 4 days and at 0.. 1.8 M (Han et al. the laccase at 1.5 mg/ml did not display any blocking activity.5 mg/ml led to a complete inhibition of virus entry after seven days of incubation..0. 2010). Extracts of mycelia derived from edible mushrooms have been reported to be effective as mucosal adjuvants for intranasal influenza vaccine against variant H5N1 influenza viruses (Ichinohe et al.. lucidum contained flavonoids. 2012a) and Pleurotus cornucopiae (Wong et al. 2010). 2010). A laccase with HIV-1 reverse transcriptase inhibitory activity has recently been isolated from fresh fruiting bodies of Lentinus edodes (Sun et al. antioxidant and HIV-1 reverse transcriptase inhibitory activities from the fruiting bodies of the abalone mushroom Pleurotus abalonus has also been reported (Wang et al. The results suggested that P. A polysaccharide with antiproliferative.25 and 1. ethanol. Antiproliferative and HIV-1 reverse transcriptase inhibitory activities have also been demonstrated from dried fruiting bodies of Hericium erinaceum (Li et al. however.hepatitis C virus HCV did not protect the cells from HCV attack and entry. while direct interaction between HCV and the laccase at the concentrations of 2. 2011).75. water. hypoglycemic. 2010). The extract of G. iso-sinensetin and dimethylguanosine from fruiting bodies of Cordyceps militaris have been shown to have antioxidant and HIV-1 protease inhibiting activities (Jiang et al. terpenoids. Schizolysin. linteus extract inhibits viral glycoprotein expression on cell surfaces through inhibition of trafficking processes rather than glycoprotein synthesis (Doseung et al. 2011b). phenolics.5 mg/ml after the second dose of treatment for another 4days (El-Fakharany et al.. a viral glycoprotein. 80 ... a hemolysin from the split gill mushroom Schizophyllum commune has been shown to inhibit HIV-1 reverse transcriptase with an IC50 of 1. and alkaloids. The laccase was capable of inhibiting HCV replication in infected HepG2 cells at 1. 2011).25 and 1.. 2011). Crude dichloromethane. 1.0 and 2.. and polysaccharide extracts of Ganoderma lucidum all suppressed HPV 16 E6.0 and 1. Lentinus tigrinus (Xu et al. with the dichloromethane extract being the most active. A methanol extract of Phellinus linteus has been reported to inhibit the trafficking process of Newcastle disease virus hemagglutinin-neuramidase. while adenosine.. in virusinfected baby hamster kidney cells. although it is unknown which compounds in the extract were responsible for the anti-viral effects (Lai et al...

Some side effects were observed at the highest dosages used. while the others were inactive. Two of the sterols showed a potent inhibitory effects while preserving the high viability of the Raji cells (Akihisa et al. which were not present when infusion was undertaken over a shorter period. also known as the sun mushroom. Anti-viral activities of Agaricus blazei Murill have been demonstrated against cytopathic effects induced by western equine encephalitis (WEE) virus by the mycelial fractions but not those of fruiting bodies (Sorimachi et al. The anti-viral effects of mushrooms do not seem to be related to viral adsorption or 81 . isolated from the nonsaponifiable lipid fraction of the dichloromethane extract of Hypsizigus marmoreus. The seven sterols and three polyisoprenepolyols were further evaluated for their inhibitory effects on Epstein-Barr virus early antigen (EBVEA) activation induced by the tumour promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) in Raji cells. have been tested for their anti-tubercular activity against Mycobacterium tuberculosis strain H37Rv using the Microplate Alamar Blue Assay (MABA). 2001).Anti-tubercular activity and an inhibitory effect on Epstein-Barr virus activation of sterols and polyisoprenepolyols from an edible mushroom. 2005). Seven sterols and eight polyisoprenepolyols. Proteins.. a betaglucan from Lentinus edodes. Six of the sterols and two of the polyisoprenepolyols showed a minimum inhibitory concentration (MIC) in the range of 151mg/ml. 2007). 9. Hypsizigus marmoreus (Buna-shimeji) have been reported..1 Summary of Anti-Viral Properties Two Phase I/II trials in HIV-positive patients have been undertaken with lentinan. Inhibitory effects on hepatitis B and herpes simplex virus type I have also been reported. Isolated polysaccharides (PLS) from the fruiting body of Agaricus brasiliensis (previously named Agaricus blazei ss Heinem). The extracts had little effect on reducing viral adsorption and did not show any virucidal effect.. the two enzymes of paramount importance to the life cycle of the HIV. peptides and polysaccharopeptides from mushrooms have been reported to be capable of inhibiting human immunodeficiency virus type 1 (HIV-1) reverse transcriptase and protease. have been shown to have anti-viral activity and were more effective when added during poliovirus infection. suggesting that they may act at the initial stage of the replication of poliovirus (Faccin et al.

1 In vitro studies (human cell lines) Maitake mushroom D-fraction in combination of interferon (IFN)-alpha has been shown to potentiate the anticancer activity of IFN-alpha in bladder cancer T24 cells in vitro.e.1. 10.. linolenic acid. 2010).1 Animal model studies Extracts from Agaricus bisporous mushrooms have been suggested as potential breast cancer chemopreventive agents. they do not kill the virus). from Cordyceps militaris. Cordycepin treatment.2.2 Breast Cancer 10. The interaction of linoleic acid and conjugated linoleic acid with aromatase mutants 82 . however a number of studies have reported inhibitory effects at the initial stage of virus replication. which was largely due to G2/M-phase arrest (Lee et al. at a dose of 200 mM (IC50) during cell-cycle progression resulted in a significant and dosedependent growth inhibition. as they suppress aromatase activity and estrogen biosynthesis. Cordycepin (3'-deoxyadenosine)..virucidal effects (i. A study has evaluated the activity of mushroom extracts in the estrogen receptorpositive/aromatase-positive MCF-7aro cell line in vitro and in vivo and found the major active compounds to be unsaturated fatty acids such as linoleic acid. and conjugated linoleic acid. Anti-tumour potential of the medicinal mushrooms Pleurotus florida and Calocybe indica against T24 bladder cancer cell lines have also been demonstrated (Selvi et al. Effects on Carcinogenesis 10.1 Bladder Cancer 10. has been shown to have anti-tumor effects in two different bladder cancer cell lines. 5637 and T-24 cells. 10. 2011). The combination of IFN-alpha 2b (10 000 IU/mL) and Maitake mushroom D-fraction (200 g/mL) reduced growth in T24 cells by ~75% by an induction of G1 arrest with DNAdependent protein kinase activation (Louie et al. 2009d)..

Whereas these results suggest that these two compounds bind to the active site of aromatase. with Maitake and Oyster mushrooms being the most effective. In situ aromatase activity and cell proliferation were measured using MCF-7aro. Oyster (Pleurotus ostreatus) and White Button (Agaricus bisporus) mushrooms significantly reduced cellular proliferation in MCF-7 human breast cancer cells by up to 33%. A study of the effects of Ganoderma lucidum (Basidiomycetes) polysaccharide (GL-PS) extract on tumor volume and T(CD4+/CD8+) ratio of tumour infiltrating lymphocytes (TILs) in breast cancer bearing mice has indicated that GL-PS (100mg/kg/day) could effectively increase the delayed type hypersensitivity response against sRBC in BALB/c mice.2.. Furthermore... the physiologically relevant aromatase inhibitors in mushrooms are most likely conjugated linoleic acid and its derivatives. Maitake also 83 . 10. 2001). the inhibition kinetic analysis indicated that they are non-competitive inhibitors with respect to androstenedione. intraperitoneal injection of this extract in breast cancer bearing mice could increase T-cell infiltration into the tumour. Phytochemicals in the mushroom aqueous extract inhibited aromatase activity and proliferation of MCF-7aro cells. 2006). These results suggest that diets high in mushrooms may modulate the aromatase activity and function in chemoprevention in postmenopausal women by reducing the in situ production of estrogen (Grube et al. As only conjugated linoleic acid was found to inhibit the testosterone-dependent proliferation of MCF-7aro cells. Aqueous extracts Maitake (Grifola frondosa). 2006). The studies showed that the mushroom extract decreased both tumor cell proliferation and tumour weight with no effect on the rate of apoptosis (Chen et al.2 In vitro studies (human cell lines) Estrogen is a major factor in the development of breast cancer and in situ estrogen production by aromatase/estrogen synthetase in breast cancer plays a significant role in tumour proliferation. suggesting a potent immunomodulatory effect (Mojadadi et al. The in vivo action of mushroom chemicals was shown using nude mice injected with MCF-7aro cells.expressed in Chinese hamster ovary cells showed that these fatty acids inhibited aromatase with similar potency and that mutations at the active site regions affect its interaction with these two fatty acids. Crimini (Agaricus bisporus). an aromatase-transfected breast cancer cell line. Portabella (Agaricus bisporus). An aqueous extract of Agaricus bisporus has been shown to suppress aromatase activity in a dose-dependent manner.

An array of low molecular weight compounds (including phenolic acids. and the potential 84 . has also been shown to have a significant and dose-dependent inhibitory effect on the proliferation of MCF-7 breast cancer cells (Wu et al. Ganoderma lucidum (Reishi) selectively inhibits cancer cell viability in inflammatory breast cancer although it does not affect the viability of noncancerous mammary epithelial cells. Coprinus comatus. Flammulina velutipes (CME.significantly induced apoptosis and cytotoxicity in these human breast cancer cells (Martin and Brophy.) Pers..and CME-treated cells and nearly completely inhibited (99%) by FVE treatment. and Flammulina velutipes contain potent anti-tumour compounds for breast cancer (Gu and Leonard. invasion and metastasis. Reishi decreased the expression of genes involved in cancer cell survival. Coprinellus sp.breast cancer cells. 2011). MCF-7 tumour colony formation rate was reduced by 60% in CCE. induction of rapid apoptosis (cell death) on both ER+ and ER. regardless of the hormone receptor status of the cancer cells. Another study in MCF-7 breast cancer cells has shown that Coprinus comatus (OFMull. tocopherols. sugars and fatty acids) from wild mushrooms have been used in molecular docking experiments against three known protein targets involved in breast cancer (aromatase. These results suggest that the mushroom species Coprinus comatus. 2010) with the activation of apoptosis possibly being mediated via BAK-1 gene activation (Soares et al. The anti-proliferative and cytotoxic activities of the three mushroom extracts were dose-dependent.. whereas it increases the expression of IL8 (Martinez-Montemayor et al. Coprinellus sp. 2011). Screening of 38 species of edible mushrooms on human estrogen-receptor positive (ER+) (MCF-7) and estrogen-receptor negative (ER-) (MDA-MB-231. carotenoids. 2011). The degree of produced cytotoxicity on ERbreast cancer cells was very high.cells. estrone sulfatase and 17beta-HSD-1) using docking software. (Agaricomycetideae).: Fr. flavonoids. Reishi has been shown to inhibit cell invasion and disrupt the cell spheroids that are characteristic of inflammatory breast cancer. Mushroom extracts CME and FVE induced a rapid (within 5 hours) apoptosis on MCF-7 and MDA-MB-231 cells. also called the Shaggy Inc Cap Medicinal Mushroom.. have anti-tumour activities including marked growth inhibition of both ER+ and ER. The estimated inhibition constants for the low molecular weight compounds. CCE and FVE. contains potent compounds capable of inhibiting NF-kappa B function that may also act as an antitumor agent (Asatiani et al.. 2006). 2007b). and significant inhibition of MCF-7 tumour colony formation in vitro. proliferation. respectively).. BT-20) breast cancer cells showed that water-based extracts of three mushroom species. The cultivated mycelium of Cordyceps sinensis (Cs).

and inhibited NF-kappaB binding and activation in a dose-dependent manner. Ganoderma lucidum suppresses the invasive behaviour of breast cancer cells by inhibiting the transcription factor NF-kappaB. followed by the inhibition of cdk4. inhibits cell proliferation and colony formation in MCF-7 human breast cancer cells. GDNT also inhibited invasive behavior (cell adhesion. The compounds 4-Ocaffeoylquinic. which was the result of the downregulation of expression of NF-kappaB-regulated cyclin D1.. and apoptosis induced by GADM may be partially due to GADM-induced DNA damage of the breat cancer cells (Wu et al. 2011). 2011a).structure-activity relationships for the compounds were determined... Froufe et al. A. These data suggest that the anti-metastatic activities of Antrodia camphorata against human breast cancer cells are mediated through suppression of the MAPK signaling pathway (Yang et al. Ganoderic acid DM (GADM). p38.. Ganoderma lucidum has been shown to suppress phosphorylation of Akt on Ser473 and downregulate the expression of Akt. Ganodermanontriol (GDNT). GDNT suppressed expression of the cell cycle regulatory protein CDC20. and JNK1/2. 2012). which is over-expressed in pre-cancerous and breast cancer cells compared to normal mammary epithelial cells. These results suggest that Ganoderma lucidum inhibits the growth of MDA-MB-231 breast 85 . a triterpenoid isolated from Ganoderma lucidum. It has been shown that Ganoderma lucidum inhibits proliferation of breast cancer MDA-MB-231 cells by downregulating Akt/NF-kappaB signaling. which results in the inhibition of NFkappaB activity in MDA-MB-231 cells. cell migration. and also over-expressed in tumors when compared to the tissue surrounding the tumor in specimens from breast cancer patients. The biological effect of Ganoderma lucidum was demonstrated by cell cycle arrest at G0/G1. 2012).. and cell invasion) through the suppression of secretion of urokinase-plasminogen activator (uPA) and inhibited expression of uPA receptor (Jiang et al. a Ganoderma alcohol is able to suppress proliferation (anchorage-dependent growth) and colony formation (anchorage-independent growth) of human breast cancer cells MDA-MB-231. 2011. Antrodia camphorata has been shown to promote cell cycle arrest and apoptosis of human estrogen-nonresponsive MDA-MB-231 cells and to markedly inhibited the invasion/migration of highly metastatic MDA-MB-231 human breast cancer cells. camphorata suppressed the phosphorylation of ERK1/2. naringin and lycopene were the top-ranked potential inhibitors for aromatase. The mechanisms involved G1 cell cycle arrest. estrone sulfatase and 17beta-HSD1 which are protein targets in breast cancer (Froufe et al.

F and H from Ganoderma lucidum on highly invasive human breast cancer cells.. lucidum inhibited the oxidative stress-induced invasive behaviour of breast cancer cells by modulating Erk1/2 signaling and could possibly be considered as an antioxidant in adjuvant cancer therapy (Thyagarajan et al.. which resulted in the down-regulation of expression of c-fos. lucidum on oxidative stress-induced metastatic behaviour of poorlyinvasive MCF-7 breast cancer cells has also been studied and it has been shown that G. which is involved in hormonal signalling cascades. lucidum extract (GLE) on cell proliferation (anchorage-dependent growth) as well as colony formation (anchorage-independent 86 . lucidum on cell migration was mediated by the suppression of secretion of interleukin-8 from MCF-7 cells exposed to oxidative stress. An aqueous extract of Cordyceps militaris (AECM) has been shown to induce apoptosis via the inhibition of Akt activation in a time-dependent manner. ganoderic acid A. lucidum inhibits proliferation of human breast cancer cells and contains biologically active compounds with specificity against the estrogen receptor and NF-kappaB (transcription factor) signalling (Jiang et al. G. A further study by the same group has also shown that an extract from green tea (GTE) increased the anti-cancer effect of G. lucidum could be promising natural agents for further study of invasive breast cancers (Jiang et al. 2004a). the same group reported the effects of the structurally related lanostane-type triterpenes.. and in the inhibition of transcription factors AP-1 and NF-kappaB. 2006). The effect of G. lucidum inhibited oxidative stress-induced migration of MCF-7 cells by the downregulation of mitogen activated protein kinase (MAPK) signalling. A subsequent study by the same group on the proliferation of human estrogen-dependent (MCF-7) and estrogen-independent (MDA-MB-231) breast cancer cells has reported that G. These results suggest that G.cancer cells by modulating Akt/NF-kappaB signaling and could have potential therapeutic use for the treatment of breast cancer (Jiang et al. The data suggested that the apoptopic effect may relate to the activation of caspase-3 and mitochondria dysfunctions that correlate with the inactivation of Akt (Jin et al. 2008). 2008).. More recently. Hydroxylated triterpenes from G.. 2006). The activity of ganoderic acids is linked to the hydroxylation in the triterpene lanostane structure. The biological effect of G. lucidum suppressed oxidative stress stimulated phosphorylation of extracellular signal-regulated protein kinases (Erk1/2).

The effect was mediated by the down-regulation of expression of the oncogene c-myc in MDA-MB-231 cells. 2004). Leucoagaricus americanus. Cell cycle analysis revealed that the fraction induced cell cycle arrest by significant decrease of the S phase. The data suggest that inhibition of growth in tumour cells by the Shiitake mushroom extract may result from an induction of apoptosis (Fang et al. Approximately 50mg/L of the fraction induced apoptosis in 50% of the population of four human tumour cell lines and the fraction-induced apoptosis may have been mediated through the pro-apoptotic bax protein which was up-regulated. An apoptopic effect in the human breast cancer cell line ZR-75-30 of a polysaccharopeptide from Coriolus versicolor has also been reported (Wan et al. (Thyagarajan et al. Extracts from Lentinula edodes (Shiitake) have been widely reported to have anti-tumour activity... p21.. A 51% anti-proliferative effect occurred at the highest concentration of the fraction (800mg/L). Further fractionation of the alcohol extract revealed that the ethyl acetate fraction inhibited both cell lines in a dose-dependent manner from 2 to 40mg/ml (Lu et al. Inonotus obliquus. However. Lentinus edodes. An ethyl acetate fraction from Shiitake (Lentinus edodes) mushrooms has been investigated using two human breast carcinoma cell lines (MDA-MB-453 and MCF-7). Phellinus linteus has also been shown to suppress growth. Compared to malignant tumour cells. While Ganoderma lucidum has shown significant inhibitory effects on NF. 2008). 2006). this activity has been shown to be host-mediated and not by direct 87 . A. and two myeloma cell lines (RPMI-8226 and IM-9). and cdk4 expression. other mushrooms which have also been reported to produce biologically active substances and have demonstrated in vitro and in vivo breast cancer inhibitory activity are Agaricus bisporus. Trametes versicolor.growth) of breast cancer cells. 2008). cyclin D1. 2007). non-malignant cells were less sensitive to the fraction for the suppression of cell growth and regulation of bax. Pleurotus ostreatus and Sparassis crispa (Petrova et al. brasiliemis. which was associated with the induction of cdk inhibitors (p21) and the suppression of cdk4 and cyclin D1 activity.. angiogenesis and invasive behaviour of breast cancer cells (Sliva et al.kappa B activity in breast cancer cells.. Concentration-dependent anti-proliferative effects of the fraction were observed in all cell lines. one human non-malignant breast epithelial cell line (MCF-10F). 2005). Grifola frondosa.. An alcohol extract from the spore of Ganoderma lucidum has been shown to inhibit the in vitro proliferation of human umbilical vein endothelial cells and MDA-MB-231 human breast cancer cells.

Hispolon extracted from Phellinus linteus has also been shown to have antiproliferative effects in breast and bladder cancer cells (Lu et al. Ovarian. It appears that P. 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..3 Cervical. MDA-MB-231) and colon cancer (HT-29. the difference being that there was no significant suppression on normal cells with the latter. A study (Israilides et al.ostreatus was associated with the cell cycle arrest at G0/G1 phase in MCF-7 and HT-29 cells. In addition to the direct inhibition of the proliferation of human breast cancer cells in vitro.cytotoxic activity to cancer cells.ostreatus also induced expression of the tumour suppressor p53 and cyclin-dependent kinase inhibitor p21(CIP1/WAF1). P. ostreatus suppresses the proliferation of breast and colon cancer cells via a p53-dependent as well as a p53-independent pathway (Jedinak and Sliva. the Lentinula edodes extract had immuno-stimulatory properties in terms of mitogenic and co-mitogenic activity in vitro. 2008) has demonstrated cytotoxic and cell growth inhibitory (cytostatic) effects of aqueous extracts of the mushroom on the MCF-7 human breast adenocarcinoma cell line. Pleurotus ostreatus (Oyster mushroom) has been shown to suppress proliferation of breast cancer (MCF-7. 10.3. 88 . Endometrial Cancer 10. Flow cytometry revealed that the inhibition of cell proliferation by P. 2008).. 2009).. without affecting proliferation of epithelial mammary MCF-10A and normal colon FHC cells. Furthermore. 2009).1 Animal model studies Protein extracts of Lentinus edodes C91-3 fermentation broth administered to mice with cervical cancer prolonged the lifespan of tumour-bearing mice significantly and killed cervical cancer U14 cells in vitro (Liu et al. mycelial extracts did not induce any cytostatic effect in both cancer and normal cell lines based on a DNA synthesis assay. The effect was demonstrated with fruit body and mycelial extracts. HCT-116) cells.

. Ethanol and hot water extracts of Pleurotus ferulae have been shown to have antitumourigenic properties in human cervical cancer cell lines and in human lung cancer cell lines. An anti-proliferative effect of ethanol and water extracts of Pleurotus tuberregium against HeLa cervical cancer cells has also recently been reported (Maness et al.. When A549. Chemopreventive activities were demonstrated by suppression of oxidative stress via the induction of antioxidant SOD and catalase as well as the phase II detoxification enzyme NAD(P)H:quinone oxidoreductase 1 (NQO1) and glutathione S-transferase PI (GSTP1) via the Nrf2 mediated signaling pathway known to provide chemoprotection against carcinogenicity (Hsieh and Wu.3.. Ganoderma lucidum has also been shown to inhibit cell growth and disruption of cell cycle progression via down regulation of cyclin D1 in the ovarian cancer cell line OVCAR-3. The anti-proliferative effect was via an induction of apoptosis (Ren et al. 2010d). 2011). the ethanol extracts showed strong cytotoxicity against A549 cells at concentrations over 10mg/mL and against SiHa and HeLa cells at over 40mg/mL (Choi et al.2 In vitro studies (human cell lines) Polysaccharides from the Lingzhi (Ganoderma Lucidum) have been shown to decrease CyclinB1 mRNA expression in cervical cancer CaSki cells and inhibit CaSki and HeLa cell proliferation (Chen et al.10. 2011). Ganoderma lucidum (Lingzhi) polysaccharides have also been shown to have an inhibitory effect on cervical cancer cells (CA Ski and HeLa cells) (Chen et al... An anti-proliferative effect of clitocine from the mushroom Leucopaxillus giganteus on human cervical cancer HeLa cells has also ben reported. SiHa and HeLa cells were incubated with different concentrations of ethanol and hot water extracts. 2010d). 2008a). 89 . 2004a).

ostreatus may prevent inflammation-associated colon carcinogenesis induced by 2amino-1-methyl-6-phenylimidazo[4. 2011). A further study by the same group also showed that the antiinflammatory activity of Pleurotus ostreatus is mediated through the inhibition of NFkappaB and AP-1 signaling (Jedinak et al.2-dimethylhydrazine (DMH) than mice treated with DMH alone.4 Colon / Colorectal Cancer 10. and inhibition of angiogenesis have all been reported to be involved in the mechanisms affecting colon cancer cells and reduction of tumor size in mice (Kim et al. 2011a). incidence of colon tumors and high grade dysplasia was reduced by 50 and 63% only in the 500 mg/kg dose (Jedinak et al. via combined modulatory mechanisms of inflammation and tumor growth via suppression of COX-2. Induction of natural killer (NK) activity. Ki-67 and cyclin D1 expression in mice. and inhibition of inflammation (Lavi et al. There is epidemiological evidence that populations with high faecal beta-glucuronidase activity have greater risk of colon cancer than populations with low faecal betaglucuronidase.. and of microadenomas.. 90 . F4/80... 2011b). Dietary administration of the fruiting body extract or mycelia extract of the edible mushroom Pleurotus pulmonarius to mice reduced the formation of aberrant crypt foci. induction of apoptosis. which precedes colorectal cancer. lucidum had significantly fewer aberrant crypts after injections of 1. However.4.10.1 Animal model (mouse) studies Treatment of mice with Pleurotus ostreatus at 100 and 500 mg/kg has suggested that P. This relationship has been investigated using the mousedimethylhydrazine colon carcinogenesis model and a fraction of Ganoderma lucidum which is a beta-glucuronidase inhibitor. 2010). activation of macrophages.5-b]pyridine (PhIP) and promoted by dextran sodium sulfate (DSS). The extracts inhibited colitisassociated colon carcinogenesis induced in mice through the modulation of cell proliferation. The treatments significantly lowered the expression of proliferating cell nuclear antigen and increased the number of cells undergoing apoptosis in the colon as well as inhibiting the expression of the proinflammatory cytokine TNF-alpha in colonic tissue. Mice with low faecal beta-glucuronidase activity induced by consumption of an ether fraction of G.

The findings demonstrated that SY-1 inhibited human colon cancer cell proliferation through inhibition of cell growth and anchorage-independent colony formation (Lien et al. Shiitake at 4% intake elicited a reduction in colon tumour multiplicity. A diet containing either 10% pleuran or 10% cellulose was compared with a 91 ..7-Dimethoxy-5-methyl-l. Consumption of 1% Shiitake stimulated growth of invasive adenocarcinomas in the mid colon and favoured a non-significant increase in median frequency of aberrant crypt foci in this same region. The authors suggested a stimulatory action of 1% Shiitake on rat colon tumourigenesis which is puzzling as the data were not statistically significant. However..2 Animal model (rat) studies Intake of dry powdered Lentinula edodes (Shiitake) has been reported to have no effect on the relative incidence of tumours in the colon or small intestine (duodenum) in azoxymethane-treated SpragueDawley rats. The effect of pleuran (beta-1. 1995). 2009). via activation of cell-mediated immunity (Masuda et al. SY-1 treatment did not induce significant changes in G0/G1 phase cell-cycle regulatory proteins in normal human colonic epithelial cells (FHC). In contrast. In contrast.. the inhibitory actions of 4% Shiitake mushroom on the indices of rat colon tumourigenesis were statistically validated (Frank et al. while not affecting the proliferation of colon-26 cells in vitro.supporting the hypothesis that the ether fraction of G. 2006). 4.4.3-D-glucan isolated from the Oyster mushroom Pleurotus ostreatus) on the antioxidant status of the organism and on the development of precancerous aberrant crypt foci (ACF) lesions in the colon have been studied in the male Wistar rat. 2009). did significantly inhibit tumour growth in BALB/cA mice inoculated with colon-26 cancer cells.lucidum can provide some protection (in this animal model) against the induction of colon cancer (Kim et al. 10.3-benzodioxole (SY-1) has been shown to decrease the proliferation of human colon cancer cells (COLO 205) through G0/G1 cell-cycle arrest and induction of apoptosis.. A 23 kDa polysaccharide isolated from Grifola frondosa.

ACF lesions developed in the colon of all animals fed a cellulose-free diet. Although ACF lesions were reduced by the cellulose diet. 10. which is involved in the progression of colorectal cancer. 2009). A marked inhibitory effect was also seen on Cdk-4 and 92 . Administration of DCl extracts did not suppress 1.2-dimethylhydrazine (DMH)treated rats developed ACF mainly in the middle and distal colon..3 In vitro studies (human cell lines) Ganodermanontriol.cellulose-free diet and both were found to significantly reduce conjugated diene content in erythrocytes and in liver. respectively. The potential blocking effect of Agaricus blazei (Ab) intake on the initiation stage of colon carcinogenesis has been investigated in a short-term (4-week) bioassay using aberrant crypt foci (ACF) as a biomarker in male Wistar rats. Ziliotto et al. however. The highest average count of the most frequent small ACF lesions. No toxicity from DCl and MET extracts was observed (Ribeiro-Santos et al.4. Chemopreventive and immunomodulatory potential of methanolic (MET) and dichloromethanic (DCl) extracts of Agaricus blazei were investigated in the postinitiation stage of colon carcinogenesis in male Wistar rats. 2009). 2008).(Ziliotto et al. All 1.2-dimethylhydrazine-induced colonic aberrant crypt foci nor did it affect the crypt multiplicity. 2001). the more significant reduction statistically (>50%) was achieved with the pleuran diet (Bobek and Galbavy. and highest total count. while ganodermanontriol inhibited transcriptional activity of beta-catenin and protein expression of its target gene cyclin D1 in a dose-dependent manner. 2008.. Particularly significant was the reduction of conjugated dienes in the colon following pleuran administration. Lymphoproliferative response was slightly decreased in the initiated control group. was seen in animals fed a cellulose-free diet. Agaricus blazei intake at 5% did not alter the number of ACF induced by DMH or the proliferating cell nuclear antigen indices in the colonic mucosa. the incidence was reduced to 64% and 60% following the cellulose and pleuran diets.. The results did not confirm a chemopreventive activity of Ab on the initiation stage of rat colon carcinogenesis (Ziliotto et al. but the highest dose of MET significantly reduced the development of preneoplastic lesions in the colon and liver. 2008) (Ziliotto et al. which was restored by treatment with MET. a lanostanoid triterpene from Ganoderma lucidum has been shown to be able to modulate of the beta-catenin pathway. Ganoderma lucidum inhibited proliferation of HCT-116 and HT-29 colon cancer cells without a significant effect on cell viability.

.PCNA expression. a human colon carcinoma cell line. lucidum extracts inhibit proliferation of human colorectal cancer cells and possesses antioxidant activity (Xie et al. GA-T inhibited the nuclear translocation of nuclear factor-kappa B (NF-kappa B) and the degradation of inhibitor of kappa B-alpha (I kappa B alpha). 2010). Ganodermanontriol also caused a dose-dependent increase in protein expression of Ecadherin and beta-catenin in HT-29 cells. A polysaccharide extract of Ganoderma lucidum has also been shown to inhibit DNA synthesis in SW 480 human colorectal cancer cells and reduce the formation of DPPH radicals indicating that G. Cell aggregation and adhesion assays showed that GAT promoted homotypic aggregation and simultaneously inhibited the adhesion of HCT-116 cells to the extracellular matrix (ECM) in a dose-dependent manner (Chen et al. The extract caused no cytotoxicity in HT-29 cells at doses less than 10. and urokinase-type plasminogen activator (uPA). in a dose. inducible nitric oxide synthase (iNOS). These results indicate that GA-T effectively inhibits cancer cell invasion in vitro and metastasis in vivo (Chen et al. and suppressed the migration of 95-D cells. Ganoderic acid T (GA-T) of Ganoderma lucidum inhibited proliferation of HCT-116 cells. 2010c). a highly metastatic human lung tumor cell line.. Ling Zhi extract (LZE) is a herbal mushroom preparation that has been shown to induce apoptosis. HT-29. 2010c). Wound healing assays indicated that GA-T also inhibited the migration of HCT-116 cells in a dose-dependent manner. 2011b). Animal and Lewis Lung Carcinoma (LLC) model experiments demonstrated that GA-T suppressed tumor growth and LLC metastasis and down-regulates MMP-2 and MMP-9 mRNA expression in vivo. Increasing concentrations reduced prostaglandin E2 93 . and suppressed tumor growth in a xenograft model of human colon adenocarcinoma cells HT-29 implanted in nude mice without any side-effects and inhibited expression of cyclin D1 in tumors (Jedinak et al. 2006).. 2011). p21 and cyclin E were not affected. An anti-proliferative effect of ethanol and water extracts of Pleurotus tuberregium against HCT-116 colon cancer cells has also recently been reported (Maness et al... In addition. antiinflammatory action and differential cytokine expression during induced inflammation in the human colonic carcinoma cell line.. An extract from Ganoderma lucidum has been reported to have apoptotic and antiinflammatory functions in HT-29 human colonic carcinoma cells. whereas expression of Cdk-2.and time-dependent manner.000µg/ml. which leads to downregulated expression of matrix metalloproteinase-9 (MMP-9). In HT29 human colon cancer cells. triterpenes from Ganoderma lucidum have also been shown to induce programmed cell death (Type II-autophagy) via a mechanism involving inhibition of p38 mitogen-activated kinase (p38 F) (Thyagarajan et al.

Similar effects in the same cell line (HT-29 human colon cancer cells) have been reported for an aqueous extract of Inonotus obliquus. ABL caused no cytotoxicity to HT29. The extract inhibited cell growth in a dose- 94 . 2000).000µg/ml decreased the expression of cyclooxygenase-2 mRNA. MCF-7. but compared with the control group (0 mg ABM). 2006).. and angiogenesis via the inhibition of Wnt/beta-catenin signaling in SW480 human colon cancer cells (Song et al. Similar anti-proliferative and pro-apoptotic activities of fractions of Pleurotus ostreatus have been reported in HT-29 colon cancer cells in vitro (Lavi et al. Oral administration of ABM (up to 45 mg ABM daily for 6 weeks) did not prevent tumor growth. Caco-2 colon cancer cells by 16%. An Agaricus bisporus lectin (ABL) has been shown to inhibit incorporation of [3H]thymidine into DNA of HT29 colon cancer cells by 87%. 1993). vascular epithelial growth factor. 2011). The internalization and subsequent slow release. the tumor mass appeared to grow more slowly following ABM doses of 4.. Among 42 cytokines tested by protein array in this study.. reflects the tendency of lectins to resist biodegradation and implies that other endogenous or exogenous lectins may be processed in this way by intestinal epithelial cells (Yu et al... Similar inhibition of proliferation of HT29 cells by ABL was found. and platelet-derived growth factor.000 µg/ml to HT-29 cells reduced the expression of interleukin-8. These results suggest that LZE has pro-apoptotic and anti-inflammatory functions. and Rama-27 rat mammary fibroblasts by 55% when the cells were grown for 24h in serum-free medium.production. and inhibition of proliferation in HT29 cells was reversible after removal of the lectin (Yu et al. LZE at a concentration of 5. as well as inhibitory effects on cytokine expression during early inflammation in colonic carcinoma cells (Hong et al. 2011b). The effects of an extract of Agaricus blazei Murrill (ABM) has been evaluated on HT-29 human colon cancer cells in severe combined immunodeficiency (SCID) mice. LZE treatment induced apoptosis by increasing the activity of caspase-3. and Rama27 cells.5 and 45 mg) (Wu et al. supplementation of LZE at doses of 500 and 5. MCF-7 breast cancer cells by 50%. Phellinus linteus has been reported to inhibit tumor growth. with little degradation of the lectin. The reversibility of the anti-proliferative effect of Agaricus bisporus lectin was associated with its release from cancer cells after internalization. macrophage inflammatory protein 1-delta. invasion.. but increased nitric oxide production. 2004).

"primed" lymphocytes. One group was not fed (control) and the second group was prefed with lentinan for 7 days prior to inoculations with the cancer cells. The results suggest that the extract would be useful as an antitumor agent via the induction of apoptosis and inhibition of the growth of cancer cells through up-regulation of the expression of proapoptotic proteins and downregulation of antiapoptotic proteins (Lee et al. Six established human colon-carcinoma cell lines segregated into three groups of different degrees of differentiation were used in this study. 2002). Splenic-sympathetic nerve activity (SNA) was suppressed by an intraduodenal Lentinus edodes injection in urethane-anesthetized rats. This was followed by inoculation of the human colon-carcinoma cell lines into these mice.dependent manner.. The size of the tumours that developed was rated after 1 month. the apoptotic cell percentage was closely associated with down-regulation of Bcl2 and up-regulation of Bax and caspase-3. The findings suggested that Lentinus edodes has an inhibitory effect on tumour 95 . In addition. Ergosterol peroxide appeared to suppress cell growth and STAT1 mediated inflammatory responses by altering the redox state in HT29 cells (Kobori et al. when given passively to immuno-deficient mice. and this inhibition was accompanied by apoptotic cell death. were able to retard the development of tumours in these mice (Ng and Yap.7 macrophages and the growth of HT29 human colon adenocarcinoma cells. 2009c). The study concluded that the anti-tumour property of lentinan was maintained with oral administration.. Further investigation on the effectiveness of the extracted lentinan was then performed using human colon-carcinoma cell lines in mice. Follow-up investigation proceeded with the use of nude mice (athymic). which significantly inhibited increases in the tumour volume of human colon and breast cancer cells implanted in athymic nude mice. in contrast to the larger tumours formed in nude mice without lymphocyte inoculation. Much smaller tumours were formed in nude mice inoculated with lymphocytes. A study on the action of lentinan (extracted from Shiitake mushrooms (Lentinus edodes) has been conducted using murine lymphoma (K36) cells in a AKR mouse model. Significant regression in tumour formation was observed in prefed mice compared to control (unfed) mice when K36 or human colon-carcinoma cells were used. In addition. 2007). Significant reductions in the size of the tumours were observed in mice prefed with lentinan. Lymphocytes extracted from AKR mice prefed with lentinan for 7 days were inoculated into the nude mice. Ergosterol peroxide from mushrooms has been shown to suppress inflammatory responses in RAW264.

proliferation, possibly via a reduction in NK cytotoxicity through the suppression of splenicSNA (Shen et al., 2009).

10.5 Gastric Cancer
10.5.1 Animal model studies
The effects of natural polysaccharides isolated from
Phellinus gilvus (PG) in vitro and in vivo against
gastric cancer have been evaluated. PG decreased
cell proliferation and increased cell apoptosis in a
dose-dependent manner in vitro and also led to a
marked inhibition of tumour growth and significant
decrease in the incidence of peritoneal
carcinomatosis. Histological analysis of the tumour confirmed a significant increase in
tumour cell apoptosis by PG, indicating reduced tumour cell proliferation. The data
showed that polysaccharides isolated from PG significantly inhibited tumour growth and
metastasis in an orthotopic model of human gastric adenocarcinoma, without detectable
adverse effects (Bae et al., 2006).
Toth and co-workers have recently reported the inhibition of intestinal cancer by a hot
water extract of the Coriolus versicolor (Turkey Tail) mushroom in C57bl/6j-Apc(Min) mice
(Toth et al., 2007).

10.5.2 In vitro studies (human cell lines)
The induction of apoptosis by extracts of Ganoderma lucidum has previously been
reported, however, more recent data have proposed that the mechanisms involved (at
least in human gastric carcinoma cells) involve caspase pathways which are associated
with inactivation of the Akt signalling pathway (Jang et al., 2010b).
Recombinant Lz-8 (rLz-8), a protein from Ganoderma lucidum induced endoplasmic
reticulum stress-mediated autophagic cell death in the human gastric cancer cell line
SGC-7901, but caspase inhibitors did not prevent rLz-8-induced cell death, and therefore

96

the autophagic response induced by rLz-8 is independent of caspase activation (Liang et
al., 2012).
Induction of apoptosis in human gastric epithelial AGS cancer cells by an aqueous extract
of Agaricus blazei has been demonstrated. It was found that an Agaricus blazei extract
could inhibit cell growth in a dose-dependent manner, which was associated with the
arrest of G2/M phase and the induction of apoptotic cell death via caspase-3 activation
(Jin et al., 2006).
An exopolysaccharide produced from the medicinal mushroom Fomes fomentarius, has
been reported to have a direct anti-proliferative effect in vitro on SGC-7901 human gastric
cancer cells in a dose- and time-dependent manner (Chen et al., 2008).
A water-soluble extract of Grifola frondosa has been shown to inhibit the proliferation of
four human gastric cancer cell lines (TMK-1, MKN28, MKN45 and MKN74) in a timedependent manner. The inhibition was most pronounced in TMK-1 cells, which exhibited
up to 90% inhibition after treatment with 10% extract for 3 days. Induction of apoptosis
was confirmed by fluorescence-activated cell sorting analyses, while Western blot
analyses of TMK-1 cells after treatment with the extract revealed increases in
intracytoplasmic cytochrome c and cleavage of caspase-3 and poly(ADP-ribose)
polymerase, but no expression of p21 or Bax. The caspase-3 protease activities in lysates
of TMK-1 cells treated with 1% or 10% of the extract were approximately 3-fold higher
than in control cells. The data suggest that this extract from Grifola frondosa produces
potential antitumour effects on gastric cancer via an induction of apoptosis of TMK-1 cells
by caspase-3-dependent and -independent pathways (Shomori et al., 2009).

10.6 Leukemia
10.6.1 Animal model studies

The effects of a beta-glucan supplement (Lentinan)
from Lentula edodes (Shiitake) on BN rats have been
studied and in a preclinical model of acute myeloid
leukemia. BN rats supplemented daily with lentinan
exhibited weight gains, increased white blood cells,
monocytes and circulating cytotoxic T-cells, and had a

97

reduction in anti-inflammatory cytokines IL-4, IL-10, and IL-6. A combination of lentinan
with standards of care in acute myeloid leukemia, idarubicin, and cytarabine increased
average survival compared with monotherapy and reduced cachexia suggesting that
nutritional supplementation of cancer patients with lentinan would warrant investigation
(McCormack et al., 2010).

10.6.2 In vitro studies (human cell lines)
A recent study demonstrated that agaritine purified from Agaricus blazei Murrill exerts
anti-tumor activity against leukemic cells in vitro (Endo et al., 2010b). Agaritine inhibited
the proliferation of leukemic cell lines U937, MOLT4, HL60 and K562, but showed no
significant effect on normal lymphatic cells. The data also showed that this activity was
distinct from that of beta-glucan, which indirectly suppresses proliferation of tumor cells.
This conclusion of direct anti-tumor activity by agaritine against leukemic tumor cells in
vitro contrasts to the carcinogenic activity previously ascribed to it in animal studies
carried out around 20-30 years ago. A more recent study by the same group has now
shown that the mechanism by which agaritine may act in U937 leukemic cells is via the
moderate induction of apoptosis via caspase activation through cytochrome C release
from mitochondria (Akiyama et al., 2011). Induction of apoptosis and alterations in signal
transduction kinases (Akt and Erk) are also produced by active fractions from Ganoderma
lucidum on human leukemia cells (Calvino et al., 2010). Hericium erinaceus
(Yamabushitake) mushroom-induced apoptosis of U937 human monocytic leukemia cell
has been reported to be via an effect on cell proliferation that involves activation of
mitochondria-mediated caspase-3 and caspase-9 but not caspase-8 (Sung Phil et al.,
2011). Extracts from Agaricus bisporus and Phellinus linteus have also been shown to
induce proapoptotic effects in the human leukemia cell line K562 (Shnyreva et al., 2010).
Extracts from Agaricus bisporus (Jagadish et al., 2009), Agaricus blazei (Gao et al., 2007),
Hypsizigus marmoreus (Mizumoto et al., 2008) and other mushrooms have been shown to
inhibit cell proliferation of HL-60 leukemia cells and other leukemia human cell lines via the
induction of apoptosis. Mechanisms by which apoptosis is induced include down-regulation of
telomerase activity and up-regulation of mRNA expression of the caspase-3 gene (Gao et al.,
2007), regulation of Bcl-2 and caspase-3 (Jin et al., 2007), cleavage of poly (ADP-ribose)
polymerase and pro-caspase 3 (Bae et al., 2009), mitochondrial membrane potential loss and
caspase activation (Mizumoto et al., 2008), release of mitochondrial cytochrome c and
subsequent activation of caspase-9 and caspase-3 (Hsu et al., 2008b) and via the signal

98

transduction kinases Akt and Erk (Calvino et al., 2010). These extracts appear to exert tumorselective cytotoxicity, with studies reporting no significant cytotoxic effects on normal cell lines
(Lau et al., 2004).
A nonlectin glycoprotein (PCP-3A) isolated from the fruiting body of the edible golden
oyster mushroom Pleurotus citrinopileatus has been shown to stimulate human
mononuclear cells to secrete cytokines TNF-alpha, IL-2, and IFN-gamma, which
subsequently inhibited the growth of U937 human myeloid leukemic cells (Chen et al.,
2010a).
Kinase inhibitors have been used for the treatment of chronic myeloid leukemia (CML) in
humans. Despite high rates of clinical response, CML patients can develop resistance to
these kinase inhibitors mainly due to point mutations within the Abl kinase domain of the
fusion protein. A crude extract of the mushroom Daedalea gibbosa has been reported to
inhibit kinase activity of Bcr-Abl kinase, and the active component has been identified as
oleic acid (Khamaisie et al., 2011).
It is interesting to note that aqueous and aqueous/ethanolic extracts of Hericium erinaceus
(Yamabushitake) mushroom were able to induce apoptosis in U937 human monocytic
leukemia cells, however, acidic and alkaline extracts with similar proximate compositions
were both inactive (Kim et al., 2011a).

10.7 Liver Cancer
10.7.1 Animal model studies
In vivo rodent studies have reported hepato-protective
effects on both chemically-induced liver toxicity and
hepato-carcinogenesis by extracts from Agaricus blazei
(Barbisan et al., 2002, Pinheiro et al., 2003) and Pleurotus
pulmonarius (Wasonga et al., 2008).

99

10.7.2 In vitro studies (human cell lines)
Lucidenic acids (triterpenoids) isolated from Ganoderma lucidum (Weng et al., 2007),
hyperbranched β-glucan, extracted from Pleurotus tuberregium (Tao et al., 2006) and extracts
from Cordyceps sinensis (Wu et al., 2007b) and Chaga (Inonotus obliquus) mushrooms (Youn
et al., 2008) have been shown to inhibit the proliferation of HepG2 human hepatocellular
carcinomas. As reported above for human leukemia cell lines, such extracts appear to be have
tumor-selective cytotoxicity, without significant effects on normal human liver cell lines (Lin et
al., 2003).
Hispolon, an active phenolic compound of Phellinus igniarius, induces apoptosis and cell
cycle arrest of human hepatocellular carcinoma Hep3B cells by modulating ERK
phosphorylation. Hispolon inhibited cellular growth of Hep3B cells in a time-dependent
and dose-dependent manner, through the induction of cell cycle arrest at S phase
measured using flow cytometric analysis and apoptotic cell death. Hispolon-induced Sphase arrest was associated with a marked decrease in the protein expression of cyclins
A and E and cyclin-dependent kinase (CDK) 2, with concomitant induction of
p21waf1/Cip1 and p27Kip1. Exposure of Hep3B cells to hispolon resulted in apoptosis as
shown by caspase activation, PARP cleavage, and DNA fragmentation. Hispolon
treatment also activated JNK, p38 MAPK, and ERK expression. Inhibitors of ERK
(PB98095), but not those of JNK (SP600125) and p38 MAPK (SB203580), suppressed
hispolon-induced S-phase arrest and apoptosis in Hep3B cells. These findings establish a
mechanistic link between the MAPK pathway and hispolon-induced cell cycle arrest and
apoptosis in Hep3B cells (Guan-Jhong et al., 2011, Huang et al., 2011). Hispolon has also
been shown to suppress SK-Hep1 human hepatoma cell metastasis by inhibiting matrix
metalloproteinase-2/9 and urokinase-plasminogen activator through the PI3K/Akt and
ERK signaling pathways (Huang et al., 2010b).
A lectin isolated from Agrocybe aegerita has been shown to bind to the surface of
hepatoma cells, leading to induced cell apoptosis in vitro, and to exert an anti-hepatoma
effect in vivo via inhibition of tumor growth and extending the survival time of tumor
bearing mice (Jiang et al., 2012). Mechanistic studies of apoptosis in human
hepatocellular carcinoma cells have shown that Agaricus blazei Murill is able to act as an
enhancer to sensitize doxorubicin (Dox)-mediated apoptotic signaling, and this
sensitization can be achieved by enhancing intracellular Dox accumulation via the

100

inhibition of NFkappaB activity. These findings suggest that Agaricus blazei Murill, when
combined with low doses of Dox, may have the potential to provide more efficient
therapeutic effects against drug-resistant human hepatocellular carcinoma (Lee and
Hong, 2011).
It has recently been demonstrated that polysaccharides from Phellinus linteus (PL) inhibit
proliferation and colony formation of HepG2 and that the growth inhibition of HepG2 cells
was mediated by S-phase cell cycle arrest. Phellinus linteus also markedly inhibited
cancer cell adhesion and invasion of the extracellular matrix and PL-induced apoptosis
was associated with a reduction in B-cell lymphoma 2 levels and an increase in the
release of cytochrome c. The results suggest that PL exerts a direct antitumor effect by
initiating apoptosis and cell cycle blockade in HepG2 cells (Wang et al., 2012a).

10.8 Lung Cancer
10.8.1 Animal model studies
An in vivo study in mice with Lewis lung carcinoma treated with
an aqueous extract of Hypsizigus marmoreus showed a
significant increase in life span when given it by intraperitoneal
administration, but not as much by oral administration. The
extract inhibited spontaneous tumor metastasis in mice bearing
the carcinoma and significantly decreased the number of
metastasized nodules (Saitoh et al., 1997).

10.8.2 In vitro studies (human cell lines)
In vitro studies have shown that three triterpene aldehydes, lucialdehydes A - C, from the
fruiting bodies of Ganoderma lucidum, possess cytotoxicity against murine and human tumor
cells (Lewis lung carcinoma (LLC), T-47D, Sarcoma 180, and Meth-A tumor cell lines) (Gao et
al., 2002), while Phellinus linteus has been shown to mediate cell-cycle arrest at a low
concentration and apoptosis in response to a high dose in mouse and human lung cancer cells
(Guo et al., 2007). Blazein, a steroid isolated from Agaricus blazei Murrill (Himematsutake), has
also been reported to induce cell death and morphological change indicative of apoptotic
chromatin condensation in human lung cancer LU99 and stomach cancer KATO III cells (Itoh et

101

SiHa and HeLa cells) (Choi et al. Recombinant Ling Zhi-8 (rLZ-8). an extract from Lentinus edodes (0. 2008).. and an extract from Pleurotus ferulae has been reported to have cytotoxic effects on human lung cancer and cervical cancer cell lines (A549.. The antitumor effect was via a modulation of p53 via ribosomal stress. beta-(1 -> 3)-D-glucan. 102 .9 mg/kg/day. A recombinant fungal immunomodulatory protein (termed GMI). 2011). 7 times/week)has been studied using a nude mouse xenograft model. 2010). 2 times/week).9 mg/ml) and hot water extracts (0.. Combined therapy of Lentinan and S-1 markedly exerted antitumor effects on human OSCC xenografts and significantly induced apoptotic cells in tumors treated with Lentinan plus S-1. 2004a). 10.. has been cloned from Ganoderma microsporum and purified.1 mg/kg/day. GMI also inhibited the EGF-induced microfilament depolymerisation (Lin et al. Both extracts were able to induce apoptotic cell death in CAL 27 cells via the release of cytochrome c from mitochondria into the cytoplasm and activation of caspase-3 in vitro (Fan et al. an immunomodulatory protein cloned from Ganoderma lucidum (Reishi or Ling Zhi) inhibits the proliferation of A549 human lung cancer cells. an oral antineoplastic agent that can induce apoptosis in various types of cancer cells (6.7 mg/ml) of Agaricus brasiliensis Mural (ABM) caused morphological changes and significantly reduced viability of human oral cancer CAL 27 Cells after 48 h of treatment. with no loss of body weight being observed in mice treated with the combined therapy (Harada et al.9 Oral Cancer 10.1 In vitro studies (human cell lines) Ethanol extracts (0.. rLZ-8 inhibited lung cancer cell growth in vitro and also in vivo. GMI exhibited an inhibitory effect on epidermal growth factor-induced migration and invasion in A549 lung cancer cells.. The responses of human oral squamous cell carcinoma (OSCC) cells to Lentinan. 2010a). 2011a). in mice transplanted with Lewis lung carcinoma cells (Wu et al. GMI inhibited EGF-induced phosphorylation and activation of EGFR and AKT pathway kinases in a dose-dependent manner.9.al. and EGF-induced activation of Cdc42 GTPase was inhibited by GMI. alone and in combination with S-1. while GMI had little effect on the EGF-induced activation of Rac1 GTPase.

2011). 2010). cell migration and spheroid formation. Combined PSK and docetaxel treatment led to a lower decrease in number of white blood cells than docetaxel alone.. increased p53 but inhibited Akt expression (Zhao et al. the growth rate of the tumors after Phellinus linteus treatment was significantly attenuated. including a reduction in tumor proliferation and enhanced apoptosis. apoptosis and antitumor responses in transgenic adenocarcinomas of mouse prostate (TRAMP)-C2-bearing mice.11. Although Phellinus linteus treatment did not prevent the formation of the inoculated tumours. a xenograft assay. Combining PSK with docetaxel significantly induced higher tumor suppression than either treatment alone. an effect accompanied by increased numbers of tumor-infiltrating CD4+ and CD8+ T cells. In this study. induced apoptosis by activating caspase 3.10. Ganoderma lucidum also inhibited colony formation. has been shown to enhance docetaxelinduced prostate cancer tumor suppression..1Animal model (mouse) studies Polysaccharide-K (PSK)..10.1 In vitro studies (human cell lines) Ganoderma lucidum has been shown to significantly decrease ovarian cancer cell numbers in vitro in a dose-dependent manner. 10.11 Prostate Cancer 10. were undertaken to evaluate the effect of Phellinus linteus on the genesis and progression of the tumours formed from the inoculation of prostate cancer PC3 or DU145 cells. 2012). an extract of the mushroom Trametes versicolor. Ganoderma lucidum also induced cell cycle arrest at the G2/M phase. together with in vitro assays. A Phellinus linteus extract has recently been reported to sensitize advanced prostate cancer cells to apoptosis in athymic nude mice (Tsuji et al.10 Ovarian Cancer 10. but did not significantly alter T-regulatory FoxP3 mRNA expression in tumors (Wenner et al. PSK with or without docetaxel significantly enhanced mRNA expression of IFN-gamma compared to control. Apoptosis occurred with the activation of caspase 3 in the tumours formed by inoculating prostate cancer DU145 or 103 .

PC3 cells. The in vivo study suggested that Phellinus linteus attenuated tumour growth and caused tumour regression by inducing apoptosis. whereas tumour cell apoptosis was increased compared to pair-fed controls. the TCA cycle and immune response (Adams et al.. 2011a).. comatus) strain 734 was able to reduce AR levels and prostate-specific antigen gene expression in the LNCaP-treated cell line (Dotan et al. 10. 2008).2 Animal model (rat) studies The inhibitory effects of methanol extracts of 19 edible and medicinal mushrooms on 5alpha-reductase activity have been reported. significantly inhibited the testosterone-induced growth of the ventral prostate in castrated rats.11. conjugated linoleic acid (CLA) have been shown to decrease DU145 and PC3 prostate tumour size and tumour cell proliferation in nude mice treated with the mushroom extract. 10. Krast (Ganodermataceae) showing the strongest 5-alpha-reductase inhibitory activity. Prostate weight increased significantly (37%) following treatment with a Phellinus linteus extract. The results showed that Ganoderma lucidum might be a useful ingredient for the treatment of benign prostatic hyperplasia (Fujita et al. A further study from the same group 104 .3 In vitro studies (human cell lines) Altered androgen receptor (AR) activity caused by point mutations or signalling mechanisms that regulate AR function has been proposed as a key mechanism in the transition to the androgen-independent stage of prostate cancer. and in particular. lipid metabolism. A suppression of transforming growth factor-beta1 expression by 56% was observed with the mushroom extract treatment.. growth and proliferation. the stromal component of the prostate increased significantly by 80%. It has been demonstrated that a hexane extract prepared from Coprinus comatus ( C.. Gene network analysis identified alterations in networks involved in cell death. or the extract prepared from it. 2005).11. Agaricus bisporus mushroom extract and one of its major components. The treatment of the fruit body of Ganoderma lucidum. 2005). The data were in agreement with data from cultured cells. with an extract of Ganoderma lucidum Fr. It was found that this mushroom extract enlarged the prostate and therefore administration of Phellinus linteus extract should be considered carefully by those with an enlarged prostate (Shibata et al.

indicating that PSP can suppress prostate CSC properties. blazei may directly inhibit the growth of prostate cancer cell via an apoptotic pathway and suppress prostate tumor growth via antiproliferative and antiangiogenic mechanisms (Yu et al. while 100% of the mice that were fed with water only developed prostate tumors at the end of the 20 weeks. Oral supplementation with the broth of A. Treatment of the prostate cancer cell line PC-3 with PSP led to the down-regulation of CSC markers (CD133 and CD44) in a time and dose-dependent manner. presumably through oxidative stress. blazei. The pharmaceutical value of the Basidiomycota fungi Coprinus comatus has also been reviewed by the same group (Dotan et al. a polysaccharide. The effects of Agaricus blazei Murill on the growth of human prostate cancer have been examined in vitro and in vivo. 2006). PSP treatment also inhibited PC-3 cell tumorigenicity in vivo. of the Grifola frondosa (Maitake) mushroom.. blazei (with the higher ratio of beta-glucan) significantly suppressed tumour growth without inducing adverse effects in severe combined immunodeficient mice with PC3 tumor xenograft. particularly in a broth fraction. The broth of A. 2000). 2011). A. 2011b). has a cytotoxic effect. 105 . although the active components were not identified (Gu and Leonard. 2009a).. inhibited cell proliferation in both androgen-dependent and androgen-independent prostate cancer cell lines. Beta-glucan. PSP. suggesting that PSP treatment can inhibit prostate tumor formation in these mice (Luk et al. on human androgen-independent prostatic cancer PC-3 cells in vitro. that were orally fed with PSP for 20 weeks did not develop tomours.isolated 2 fractions from the same mushroom strain that inhibited AR-mediated reporter activity and reduced the levels of AR and prostate-specific antigen (PSA) transcripts in LNCaP cells. blazei induced lactate dehydrogenase leakage in three cancer cell lines. One of these fractions (F-32) also inhibited the proliferation and clonigenicity of LNCaP cells and inhibited the binding of AR to the PSA enhancer region and inhibited Akt-mediated AR phosphorylation at Ser 213 (Dotan et al... Another study in the same cell line showed similar cytotoxic effects from a water-soluble extract from Pleurotus ostreatus (Oyster). Transgenic mice (TgMAP) that spontaneously develop prostate tumors. whereas the activities of caspase 3 and the DNA fragmentation were enhanced the most in androgen-independent PC3 cells. The data suggested that the broth of A. an active component extracted from Coriolus versicolor has been reported to be effective in targeting prostate cancer stem/progenitor cells (CSCs). leading to apoptosis (Fullerton et al. 2010)..

2012). For example. capillary morphogenesis of the human aortic endothelial cells. mediated..and timedependent manner and induce apoptosis in human prostate cancer cells PC-3 (Jiang et al.Ganoderma lucidum has also been shown to inhibit proliferation in a dose.. resulting in the down-regulation of secretion of Vascular Endothelial Growth Factor and Transforming Growth Factor beta (TGF-beta1) from PC-3 cells. 2007). lucidum on these prostate cancer cells are still unclear.. 2006).. triggering an apoptotic process in androgen-insensitive (DU-145) human prostate cancer cells (Russo et al. However. lucidum inhibits prostate cancer-dependent angiogenesis by modulating MAPK (mitogen activated protein kinase) and Akt signaling and could have potential therapeutic use for the treatment of prostate cancer (Stanley et al. Phellinus linteus has been reported to sensitise apoptosis induced by doxorubicin (an anticancer drug) in prostate cancer LNCaP cells suggesting that Phellinus linteus may have therapeutic potential to augment the magnitude of apoptosis induced by anti-prostate cancer drugs (Collins et al.4-dicinnamide from the gilled mushroom Pholiota spumosa (Basidiomycetes) has also been reported to inhibit cell growth of an androgen-independent human prostate cancer (PCA) cell line by inducing apoptosis. lucidum inhibits the early event in angiogenesis. Interferon (IFN)-alpha2b has also been shown to have synergistic effects with mushroom extracts in inducing significant reductions reduction in PC-3 cell growth. the molecular mechanisms responsible for the inhibitory effects of G. 2005). These effects are caused by the inhibition of constitutively active AP-1 in prostate cancer cells. Polysaccharides and ethanol extracts of the fruiting bodies of Tremella aurantia mushrooms have also been shown to possess growth-inhibitory activity in LNCaP and PC-3 human prostate cancer cells (Kiho et al. 2010). 2010). 2008).. It has been found that G.. by the activation of caspase cascades (Russo et al. at least in part. 106 . ergosterol peroxide exerted antitumor activity in multiple myeloma U266 cells partly with anti-angiogenic activity targeting the JAK2/STAT3 signalling pathway (Rhee et al. Ergosterol peroxide derived from edible mushrooms has been shown to exert anti-tumor activity in several cancer cells... Putrescine-1. at least in part. In a recent study in human multiple myeloma U266 cells. This appears to be due to a synergistic potentiation leading to a G1 cell cycle arrest (Pyo et al. The data suggest that G. 2004b). ergosterol peroxide has been shown to attenuate the growth of prostate cells.

2 In vitro studies (animal cell lines) Lentinula edodes has been shown to reduce cell proliferation and induce apoptosis in CH72 mouse skin carcinoma cells via an induction of a transient G1 arrest with no effect in non- 107 . 2000). 1985). B-16 melanoma (B-16) and adenocarcinoma 755 (Ca-755) in the mouse. ex Fr. isolated from the culture mycelium of Flammulina velutipes (Curt. but it had no direct effect on cancer cell growth. Oral administration of proflamin produced no lethal or any other apparent adverse effect in mice (Ikekawa et al... Proflamin has been shown to be markedly effective against the syngeneic tumours. the authors reported that PL increased macrophage NO production. An acidic polysaccharide from Phellinus linteus has been shown to markedly inhibit melanoma cell metastasis in mice. the extracellular matrix.12 Skin Cancer 10. and invasion through.12. Proflamin exhibited no cytocidal effect against the cultured cell lines in vitro.it acts as an immuno-potentiator and as a direct inhibitor of cancer cell adhesion (Han et al. 2009). In addition.) Sing. Mushroom oligosaccharides that down-regulate production of immuno-suppressive cytokines by ultraviolet radiation injured keratinocytes appear to be promising agents for the prevention of environmental (sun induced) skin cancer (Pelley and Strickland. and directly inhibit cancer cell adhesion to.10.12. 2006). and has a molecular weight of ~13. 10.. An extract of Ganoderma lucidum has also been reported to reduce chemically-induced mammary adenocarcinomas in Sprague Dawley rats and skin tumours Balb/c mice (Lakshmi et al. These results suggest that Phellinus linteus has two anti-metastatic functions . The increases in median survival time of treated mice with B-16 and Ca-755 were 86% and 84%. respectively.000 Da. is a weakly acidic glycoprotein containing more than 90% protein and less than 10% carbohydrate.1 Animal model (mouse) studies Proflamin.

but increased the median survival time of mice treated with B-16 and Ca-755 by 86% and 84%. 2005).e. Similarly.1 Animal model (mouse) studies It has been suggested that synthetic agaritine (i.. 2008).tumorigenic (C50) cells (Gu and Belury. isolated from Flammulina velutipes. followed by both apoptotic and secondary necrotic cell death has been demonstrated for a methanol extract of Coriolus versicolor (Harhaji et al. and a recent review (Roupas et al. The inference for DNA damage in this study was from a result of a separate in vitro test. Another in vivo study demonstrated that crude extracts of Agaricus blazei Murrill significantly reduced DNA 108 . 1985). 2008). These results suggest that Phellinus linteus has two anti-metastatic functions—it acts as an immunopotentiator and as a direct inhibitor of cancer cell adhesion (Han et al.. proflamin.. with no apparent adverse effects (Ikekawa et al. An acidic polysaccharide from Phellinus linteus has been shown to markedly inhibit melanoma cell metastasis in mice.13. recent research (Endo et al. the extracellular matrix. 2006). not extracted from mushrooms) is quickly metabolized in mice and disappears in the plasma. exhibited no cytotoxic effects against B-16 melanoma (B-16) and adenocarcinoma 755 (Ca755) cultured cell lines in vitro. 2010b) has ascribed anti-tumor activity of agaritine (from mushrooms) against leukemic cells. 2010a) also concluded that agaritine from consumption of cultivated Agaricus bisporus mushrooms poses no known toxicological risk to healthy humans... a similar experiment with a different marker of oxidative stress did not. In contrast. with an increase in macrophage NO production but to have no direct effect on cancer cell growth.13 DNA Damage 10. reduction of cell proliferation of B-16 melanoma cells by arrest in the G0/G1 phase of the cell cycle. respectively. In contrast. whereas DNA damage after a single administration of synthetic agaritine lasts for a longer time (Kondo et al. and directly inhibit cancer cell adhesion to.. thus the authors made these comments based on their results with one particular marker only. and invasion through. 10. While data with a particular marker of oxidative stress showed this effect.

Hypsizygus marmoreus. while DNA strand breaking by the carbon-centered radical generated from 4(hydroxymethyl) benzenediazonium salt from Agaricus bisporus has been reported in the mouse (Hiramoto et al.. PPC-Pr treatment enhanced the declined levels of antioxidants and demonstrated a DNA protective effect (as determined by a Comet assay) as well as significantly increasing the survival rate of animals (Joseph et al. or Volvariella volvacea (Rocha et al. while other mushroom varieties do not. 10. No protective effects were observed with mushroom derived preparations from Flammulina velutipes. Some edible mushrooms therefore represent a valuable source of biologically active compounds with potential for protecting cellular DNA from oxidative damage. a possible chemoprotective effect of β-glucan extracted from Agaricus blazei against DNA damage induced by 109 .2 In vitro studies In vitro studies have shown that a heat-labile protein from Agaricus bisporus protects Raji cells (a human lymphoma cell line) against H2O2-induced oxidative damage to cellular DNA (Shi et al.. respectively.. have been reported from Chaga mushroom (Inonotus obliquus)(Park et al. compared with H2O2 as a positive control. Beta-glucan from Agaricus brasiliensis has been reported to be devoid of mutagenic activity and to provide a significant dose-dependent protective effect against DNA damage in the dose range 20-80 mg/ml (Angeli et al. 1995). Furthermore.damage in liver induced by diethylnitrosamine in adult male Wistar rats (Barbisan et al. 2002). Auricularia auricula. Lentinula edodes. 2006). 2012). 2003)... while an aqueous extract from Agrocybe cylindracea strain B has also been shown to protect against DNA damage in HepG2 cells (Wang et al. Similar reductions in DNA fragmentation (Comet assay). Similar protective effects against H2O2-induced oxidative damage to cellular DNA have been demonstrated with cold (20ºC) and hot (100ºC) water extracts of Agaricus bisporus and Ganoderma lucidum fruit bodies. A polysaccharide protein complex (PPC-Pr) isolated from the mushroom Phellinus rimosus has been shown to have a protective effect (at doses of 5 and 10 mg/kg body weight intraperitoneally for 5 days consecutively) against oxidative stress induced by gamma radiation (4 Gy) in Swiss albino mice. 2004).... 2011). An earlier study from the same group at the same doses of PPC-Pr had reported its effect on alleviating gamma radiation-induced toxicity in the Swiss albino mouse model (Joseph et al.13.. 2004). 2002). Pleurotus sajor-caju.

2010). but that it did protect against DNA damage via binding to benzo[a]pyrene or by the capture of free radicals produced during its activation (Angeli et al. 1999).. for tumour regression and prevention of radiation-induced cellular damage in normal tissues (Gopakumar et al. consequently increasing phagocytic capacity especially in the groups pre-treatment. Polysaccharide extracts from Se-enriched G. 2011).benzo[a]pyrene. post-treatment and pre-treatment+continuous conditions. Single-cell gel electrophoresis (comet assay) on cells of normal and tumour tissues from tumour-bearing animals treated with GLE and radiation. blazei did not have genotoxic activity but showed antigenotoxic activity (Comet assay). suggesting that supplementation increases a proliferation of monocytes. 110 . indicating preferential protection to normal tissues and possible use as an adjuvant in radiotherapy. 2004). simultaneous treatment. A water-soluble polysaccharide from Ganoderma lucidum was protective against hydroxyl radical-induced DNA strand breaks (Kim and Kim. Supplementation with Agaricus blazei. 2006). and this effect increased with increasing Se content (Zhao et al. 2008)... Supplementation caused an increase in the number of monocytes and in phagocytic activity. carried out under pre-treatment. since this mushroom was demonstrated to have a preventive effect against pre-neoplastic colorectal lesions evaluated by the aberrant crypt foci assay (Ishii et al... simultaneous and pre-treatment+continuous. Strong DNA protective effects from oxidative damage have been reported for protein extracts from selenium-enriched Ganoderma lucidum (Se-GLPr). 2009). lucidum have also been shown to protect DNA from hydroxyl radical oxidative damage in a dose dependent manner (Zhao et al. Oral administration of Ganoderma lucidum extract (GLE) to tumor-bearing Swiss albino mice along with exposure to gamma radiation has been shown to result in tumour regression. revealed that there was significant reduction in radiation-induced damage to cellular DNA in normal tissues compared to the tumour. using the comet assay (genotoxicity) and micronucleus assay with cytokinesis block (mutagenicity) in a human hepatoma cell line (HepG2) has suggested that b-glucan did not exert a genotoxic or mutagenic effect. The data suggest that A.. blazei could promote immunomodulation which can account for the destruction of cells with DNA alterations that correlate with the development of cancer. and radioprotective properties of an aqueous extract of Ganoderma lucidum against radiation-induced plasmid pBR322 DNA strand breaks have been demonstrated that may be due to inhibition of lipid peroxidation (Pillai et al. has shown that A.

14 Summary of Anti-Cancer Properties Anti-tumor effects. Anti-tumor effects of proteoglycan fractions from a variety of mushrooms. have been reported for polysaccharides extracted from various mushrooms.Polysaccharides isolated from Ganoderma lucidum have been reported to enhance the repair of radiation induced DNA strand breaks in human cells after 120min of exposure (Pillai et al. In recent years. 2010). which is then followed by NO production in macrophages via activation of the transcription factor. NF-kappaB. the anti-inflammatory and antimicrobial / viral effects described in this report may also contribute to the anti-carcinogenic effects of mushrooms and their extracts. welldesigned human clinical trials are required before the anti-cancer mechanisms and health outcomes in humans can be validated. The polysaccharides generally belong to the betaglucan family of compounds and appear to exert their anti-tumorigenic effects via enhancement of cellular immunity. a number of human trials have been undertaken and these have been described earlier in this report.. 10. Activation of NK cells is likely via interferon-gamma and interleukin mediated pathways. In addition to the apoptotic and anti-proliferative effects. While studies in human cell lines provide supporting evidence. primarily in human cell lines. involve the elevation of natural killer (NK) cell numbers and the stimulation of inducible nitric oxide (NO) synthase gene expression. Apoptosis and/or anti-proliferative effects on carcinomas and cell lines is also a mechanism shared by several mushrooms and their extracts in studies of anti-cancer effects. including Agaricus bisporus. although such direct links have not been established to date. 111 .

A study has been conducted to investigate the hypocholesterolemic effect of a hot-water fraction (HW) from cultured mycelia of Cordyceps sinensis. A similar study in mice has also reported that consumption of either a hot water extract or ethanol extract of Hericium erinaceus improved lipid metabolism in mice fed a high-fat diet. Histopathological observations indicated that the extract could effectively prevent excessive lipid formation in liver tissue (Chen et al. and increased high-density lipoprotein cholesterol. the extract decreased total cholesterol. Administration of either the water-extract or ethanol-extract with a high fat diet for 28 days resulted in a marked decrease in body weight gain. and total fat mass (Handayani et al. but decreased the very low-density lipoprotein plus low-density lipoprotein (VLDL+LDL) cholesterol level.. plasma triglyceride. 2010). 2011). Effects on Cardiovascular Health 11. The results indicated that HW in rats administered a cholesterol-enriched diet decreased the plasma cholesterol 112 . 2012b). total triglyceride. body and liver weights were not significantly different from those of the controls. Among the mice fed the cholesterol-enriched diet.11. respectively) with the cholesterolenriched diet decreased more than in the control group. and low-density lipoprotein cholesterol. HW also increased the high-density lipoprotein (HDL) cholesterol level. in a high-fat-load mouse model.. Furthermore.1 Animal model (mouse) studies A water-soluble polysaccharide extract of Pleurotus eryngii has been shown to significantly increase the activitiy of antioxidant enzymes and effectively remove free radicals in a liver-injury mouse model. The serum total cholesterol (TC) of all mice groups administered HW (150 and 300mg/kg/d. The changes in HDL-and VLDL+LDLcholesterol levels consequently decreased the atherogenic value.. In mice fed a cholesterol-free diet and those fed a cholesterol-enriched diet. fat weight as well as blood and hepatic triacylglycerol levels (Hiwatashi et al. Supplementation of rats on a high fat diet with Shiitake Mushroom (Lentinus edodes) powder resulted in negative correlations between the amount of Shiitake mushroom supplementation and body weight gain.

Ganoderma lucidum exhibited a dose-dependent antioxidative effect on lipid peroxidation and superoxide scavenging activity in mouse heart homogenate. possibly via their significant antioxidant activity (Wu et al. Agaricus sylvaticus has also been reported to prevent the onset of atheroma plaques in hypercholesterolemic rabbits (Percario et al.. Atherosclerotic lesions were significantly decreased in the 3 mushroom groups compared to the control group. 2008). Furthermore..9 mg GABA/kg) has also 113 .level. 2008).. Anti-atherosclerotic effects of Pleurotus eryngii (Eringi). beginning at a time when the animals were 10 weeks of age with well-established high blood pressure.. 2003). 2004). have been demonstrated in atherosclerosissusceptible C57BL/6J. Auricularia auricula polysaccharides have also recently been reported to have a positive effect on heart function of aged mice. 1989). Conversely. Shiitake mushroom intake did not reduce blood pressure. A single dose of gamma-aminobutyric acid (GABA) enriched Flammulina velutipes (Enokitake) powder (0. triglyceride and phospholipid in comparison to the control (Kabir and Kimura.. The authors concluded that this effect of Ganoderma lucidum may protect the heart from superoxide induced damage (Wong et al. triglyceride and phospholipid levels between the Maitake fed animals and the control. this result indicated that heart damage induced by ethanol showed a higher malonic dialdehyde level compared with heart homogenate treated with Ganoderma lucidum. 11. but significantly lowered free plasma cholesterol. involve the renin-angiotensin system (Preuss et al. Blood pressure of spontaneously hypertensive rats (SHR) has been shown to be significantly reduced by Maitake feeding for 8 weeks. There was no difference in the plasma total and free cholesterol. and Hypsizygus marmoreus (Bunashimeji). The anti-atherosclerotic effect was partially via lowering of serum total cholesterol concentrations (Mori et al. Grifola frondosa (Maitake). The 300mg/kg dose had a significant effect on the serum total cholesterol level (Koh et al. at least in part. apolipoprotein E-deficient (apoE(-/-)) mice..2 Animal model (rat and larger animal) studies Maitake mushroom extracts have been suggested to ameliorate progressive hypertension in female Sprague-Dawley rats via an effect on systolic blood pressure that may. 2010). A hot water extract from Ganoderma lucidum has been shown to have an antioxidative effect against heart toxicity in mice. 2010).

or enzyme profiles. direct bilirubin. A hypocholesterolemic effect has been shown with Oyster mushrooms (Pleurotus ostreatus) in rats with Streptozotocine-induced diabetes. creatinin. It was suggested that the serum TC decline is the action of eritadenine that is contained in the Shiitake mushroom. respectively. 114 . 47.50. blood urea nitrogen. potassium. An inhibitory activity of the angiotensin I-converting enzyme (ACE) was compared between of LE and autolyzed-LE. The hypocholesterolemic effects of Oyster mushrooms has been demonstrated to be dose-dependent (Bobek et al. total protein. 2011b). nebrodensis was acting on the atherogenic lipid profile in these hypercholesterolemic rats (Alam et al. triglyceride and phospholipid of the groups fed with LE and autolyzed-LE were lower than those of the control group. 24.91.. Essentially identical results were also reported for Pleurotus ferulae in the same animal model (Alam et al. Autolyzed-LE showed higher inhibitory activity than LE against the ACE. magnesium. inorganic phosphate. The results suggested that the hypotensive action of autolyzed-LE was due to concomitant ACE inhibitory activities of peptides and gamma-aminobutyric acid contained in higher amounts during the autolysis of LE (Watanabe et al.. 62. The serum levels of total cholesterol (TC).. but no effects were observed in rats with normal blood pressure (Harada et al. The data suggest that P. 2002).. 2011). 1990).06%. 31.(fermented-) Shiitake (autolyzed-LE) on blood pressure and serum fat levels of spontaneously hypertensive rats (SHR) have been studied. The effects of Shiitake (Lentinus edodes. with significant reductions in body weight..been shown to result in a significant lowering of systolic blood pressure ( by 30 mmHg) in spontaneously hypertensive rats (SHR). calcium. Similar results have been observed in rats with a hereditary hypersensitivity to dietary cholesterol (Bobek et al.65 and 53. and atherogenic index [(TC-HDL-C)/HDL-C] improved significantly in 21 days. LE) and autolyzed. The animals of the autolyzed-LE group showed significantly lower blood pressure compared to the control or LE group.. No adverse effects were reported on plasma albumin. phospholipids and LDL/HDL ratio by 31.01. 1991). uric acid.. 2011c). Feeding hypercholesterolemic Sprague-Dawley albino rats a diet containing 5% fruiting bodies of Pleurotus nebrodensis reduced plasma total cholesterol. triglyceride. glucose. chloride. The feeding of these mushrooms increased total lipid and cholesterol excretion in feces. Oyster mushroom (4% dry oyster mushroom fruit body) lowered cholesterol content by more than 60% in the liver although it did not significantly affect either the serum triacylglycerol level or the content in liver (Bobek et al.71. low-density lipoprotein. total lipid. sodium. total bilirubin.

.. Hiratake. Cheung. Hypocholesterolemic activity of the agent eritadenine present in Lentinus edodes has been reported (Enman et al.1.4.. 2001b). 2007).) mushroom has been demonstrated in rats (Ukawa et al.1997). Furthermore. 2000). The effects of four edible mushrooms (Shiitake. 1996a). 1996). and Enokitake (Flammulina velutipes) fiber have also been reported (Fukushima et al. Exobiopolymers (EXBP) produced from a submerged mycelial culture of Ganoderma lucidum has also bben shown to lower liver total cholesterol. The results demonstrated that mushroom fiber (and sugar beet fiber) lowered the serum total cholesterol level by enhancement of the hepatic low density lipoprotein (LDL) receptor mRNA (Fukushima et al. The Bunashimeji mushroom (Hypsizigus marmoreus) has also been shown to suppress hepatic triacylglycerols accumulation and lowers blood cholesterol levels in mice (Ohtsuki et al. In contrast to the above studies.. farm-grown Agaricus campestris in the diet of rats did not affect plasma and liver cholesterol concentrations (Beynen et al. A similar hypocholesterolemic effect of the oyster mushroom (Pleurotus ostreatus) was also observed in hamsters (Bobek et al.. 1999). 2007). and by Ganoderma lucidum in hamsters and mini-pigs (Berger et al. Eringi and Hatakeshimeji groups than that in the control group. Hatakeshimeji) on serum and hepatic lipid levels have been investigated in rats. 1996b) and Pleurotus ostreatus (Oyster mushroom) (Hossain et al. 1998. the high-density lipoprotein (HDL) cholesterol and ratio of HDL cholesterol to total cholesterol were significantly increased 115 . Hypocholesterolemic activity by Hatakeshimeji (Lyophyllum decastes Sing.9%. Shiitake (Lentinus edodes) fiber.. Similar cholesterollowering effects in rats of Maitake (Grifola frondosa) fiber. 2003). triglyceride.. 2004). 2006).. Other mushroom varieties that have been shown to have hypocholesterolemic properties include Volvariella volvacea (straw mushroom) (Cheung. 2001). 1993b) and in rabbits (Bobek and Galbavy. and lower blood lipid levels (Ohtsuki et al. and 12. respectively.. The serum cholesterol levels of the mushroom groups were also significantly lower than that of the control group showing that these four edible mushrooms suppress hepatic triacylglycerol accumulation. The results showed that the body weight and food intake of the four mushroom groups were significantly lower than those of the control group.. Eringi. The liver level of triacylglycerols was significantly lower in the Hiratake. Auricularia auricula (Tree-ear) and Tremella fuciformis (White jelly-leaf) (Cheung. and phospholipid levels by 22. 23. Plasma cholesterol concentration in rats has been shown to be reduced by feeding of mushroom (Agaricus bisporus) fibre.

8 times those in animals fed the basic feed. 1997). using the same rat model system.v.(Yang et al. It produced positive chronotropic and inotropic effects on isolated right atria and induced contraction of isolated tail artery strips. 1995). A further study by the same group.6-0. Maitake mushroom consumption has also been shown. has also shown that consumption of dried Maitake powder (mixed with a basic high-cholesterol rat chow) cholesterol. Liver lipids were also measured and the values were found to be decreased by Maitake administration. Measurement of the amount of total cholesterol and bile acid in faeces showed the ratio of cholesterolexcretion had increased 1. indicating that Maitake inhibited lipid accumulation in the body. Partial purification using dialysis and liquid chromatography revealed that the hypotensive active substances had molecular weights between 8.000 -12. An i. triglyceride and phospholipids in the serum of rats in the Maitake-feed group were suppressed by 0. Weights of liver and epididymal fat-pads were significantly lower (0. An aqueous extract of the mushroom (SME) was prepared and given through intravenous injections to normotensive rats. to have the ability to alter lipid metabolism by inhibiting both the accumulation of liver lipids and the elevation of serum lipids. ketanserin and phentolamine respectively. in Sprague-Dawley rats.000 daltons and were heat stable and resistant to trypsin digestion (Chiu et al. 2002b). 1996). The straw mushroom Volvariella volvacea has been reported to produce a hypotensive response in animals.7 times) than those in the basic feed group. injection of SME produced a hypotensive effect in rats with an ED50 of 25mg dry weight/kg body weight.30. Further studies are needed to determine the mechanism of activity of Maitake mushrooms and to establish whether their action in humans is similar to that observed in the rat model (Kubo and Nanba.8 fold and bile acid-excretion 3 fold by Maitake treatment suggesting that Maitake consumption may help to improve the lipid metabolism as it inhibits both liver lipid and serum lipids which were increased by the ingestion of high-fat feed (Kubo and Nanba. 116 . This latter contractile response was inhibited by antagonists of serotonin and alpha-adrenoceptor. The blood pressure changes produced by SME alone or in the presence of various drugs were studied... SME did not increase urinary excretion or sodium diuresis.

2011)... which are associated with cardiovascular disease (Martin. A further study by the same group reported that ergothioneine.. and glutamic acid (Kim et al. 2010b). 2006) and Hatakeshimeji (Lyophyllum decastes Sing. 2010a). Angiotensin-converting enzyme (ACE) inhibitory activity (which has an effect on blood pressure reduction) has been demonstrated in the culture broth from Flammulina velutipes (strain 414). An aqueous extract of Ganoderma lucidum has been shown to possess ACE inhibitory activity (IC50 = 50 mg/mL) in vitro (Abdullah et al. Water extracts of the P. Reactive oxygen free radicals have been reported to be important in ischemia-reperfusion injury cascades. Lentinula edodes (shiitake).) (Ukawa et al. Pleurotus ostreatus (oyster). Pretreatment with ABM extract reduced hydrogen peroxide-induced cell 117 .3 In vitro studies Agaricus bisporus (white button and crimini). 2001a).46 and 1.14 mg/ml. and Grifola frondosa (maitake) mushrooms have been shown to inhibit adhesion molecule expression and in vitro binding of monocytes to human aortic endothelial cells under pro-inflammatory conditions.85 and 2037. Production and characterization of an anti-hypertensive angiotensin Iconverting enzyme inhibitor has also been reported from Pholiota adiposa (Koo et al.11. previously reported to modulate oxidative stress. ammonium acetate. 2011a). cornucopiae fruiting body also showed a clear antihypertensive effect on spontaneously hypertensive rats at a dosage of 600 mg/kg (Jang et al. velutipes were shown to include sucrose. 2002). An extract from Hypsizygus marmoreus has also been shown to inhibit platelet aggregation induced by collagen suggesting that it may have an effect against platelet related cardiovascular disease (Park et al. increased the survival of rat cardiomyocytes (H9c2 cell line) without cytotoxicity.26 Da. an antioxidant present in edible mushrooms. and to inhibit monocyte binding to endothelial cells characteristic of early cardiovascular disease (Martin.. Two different ACE inhibitors (oligopeptides) from Pleurotus cornucopiae have been identified with IC50 values of 0. The molecular mass of the purified ACE inhibitors was estimated to be 1622. Agaricus Blazei Murill (ABM) extract. The amino acid sequences of the two purified oligopeptides were RLPSEFDLSAFLRA and RLSGQTIEVTSEYLFRH. Nutritional requirements for the production of ACE inhibitory activity from F. respectively.. 2012). was able to interrupt proinflammatory induction of adhesion molecule expression associated with atherogenesis.

Such a cholesterol-lowering effect has also recently been reported in humans. ABM may have a cardioprotective effect by increasing antioxidant activity. and fed a diet containing H. A methanol 118 . 2011). 11. erinaceus over a 23-d experimental period. Memory and learning function was examined. Mice were administered 10 g of amyloid beta (25-35) peptide intracerebroventricularly on days 7 and 14. While some studies have postulated eritadenine or angiotensin I – converting enzyme inhibitory peptides as the hypocholesterolemic agents.1 Animal model studies The effects of Hericium erinaceus on amyloid beta (25-35) peptide-induced learning and memory deficits in mice have been evaluated.4 Summary of Cardiovascular Health Plasma cholesterol in animal models has been shown to be reduced by mushroom consumption. with H. which greatly ameliorates myocardial injuries caused by myocardial ischemia-reperfusion injuries (Huang et al. Agaricus bisporus) fibre.. erinaceus preventing impairments of spatial short-term and visual recognition memory induced by the amyloid beta(25-35) peptide (Mori et al.g.. 2010a). Effects on Neurodegenerative Diseases / Cognition 12. and other biomarkers of cardiovascular risk. ABM-pretreated rats that underwent myocardial ischemia-reperfusion had greatly reduced infarct areas compared to those in the control group.damage and increased cell survival. have been demonstrated by consumption of mushroom (e. similar effects on cholesterol. 12. Cognitive enhancing and antioxidant activities of Inonotus obliquus (Chaga) have been evaluated against scopolamine-induced experimental amnesia in mice. The hypocholesterolemic effect appears to be due partly to an increased rate of low density lipoprotein (LDL) and high-density lipoprotein (HDL) catabolism. .

a peptide purified from the medicinal mushroom Cordyceps sinensis has been reported to have a neuroprotective effect in the ischemic brain. the activities of acetylcholinesterase (AChE). erinaceum and its components could be useful for preventing cerebral infarction (Hazekawa et al.. Treatment of mice with Hericium erinaceum (H. protected against focal cerebral ischemia.extract of Chaga (MEC) at 50 and 100 mg/kg doses was administered orally for 7 days to amnesic mice. The activity exhibited by the extract of Ganoderma lucidum was partially correlated to its antioxidant activity... Reactive oxygen species have been reported to be involved in the pathogenesis of a number of age-associated human health conditions. which is due to the inhibition of inflammation and increase of antioxidants activity related to lesion pathogenesis (Wang et al. anti-oxidant enzymes. To elucidate the mechanism of the cognitive enhancing activity of MEC. 2012b). by increasing nerve growth factor levels suggesting that H. MEC treatment for 7 days significantly improved the learning and memory. A significant benefit of this neuroprotective effect was a wide therapeutic time window since significant infarct volume reduction was obtained by administration. erinaceum) (300 mg/kg for 14 days) prior to middle cerebral artery (MCA) occlusion.. even after the ischemic event (Suzuki et al. 2011). The mitochondrial respiratory chain is a direct intracellular source of reactive oxygen species. 2009). The level of lipid peroxidation was significantly lowered in the Ganoderma lucidum treated group compared to the aged controls. Ganoderma lucidum (50 and 250 mg/kg) has been shown to enhance the activities of mitochondrial dehydrogenases and complex I and II of the electron transport chain in the brain of aged male Wistar rats (Ajith et al. 2011). the levels of acetylcholine (ACh) and nitrite of mice brain homogenates were evaluated. 2010). In a rat model of permanent focal cerebral ischemia (using Sprague-Dawley rats). while post-treatment (30minutes after ischemic onset) also significantly reduced cortical infarct volume. a filtrate of Phellinus linteus broth significant reduced cortical infarct volume 30 and 60 minutes before onset of cerebral ischemia compared with the control group. Cordymin. 119 .. then further studies would be warranted to evaluate possible future applications against ageing associated neurodegenerative diseases. The significant cognitive enhancement observed in mice after MEC administration was closely related to higher brain anti-oxidant properties and inhibition of AChE activity (Giridharan et al. If Ganoderma lucidum is able to improve the function of mitochondria in the aged rat brain.

Fractionation on the basis of molecular mass (MM). known as an important AD risk factor. anti-adhesion/coaggregation.. 2012c). and anti-biofilm agent(s) that may be used for protection towards caries and gingivitis. 13. Another very similar study has also shown that low molecular mass (LMM) fractions from extracts of Shiitake mushrooms (as well as from raspberry and red chicory) have been shown to be a useful source of specific antibacterial. was suppressed by the treatment of the fruiting body rather than that of mycelium demonstrating that the fruiting body resulted in a more significant improvement on working memory ability than mycelium in the AD rat model (Wang et al. 12. with the lower MM fractions showing higher activity that the high MM fractions (Daglia et al. 2011).. of water-soluble components revealed that mushroom extract had a high potential against oral pathogens.2 In vitro studies A recent study has compared the effect of the fruiting body and mycelium of Antrodia camphorata on alleviating the A-beta40-induced neurocytotoxicity in an in vitro A-betadamaged neuron cell model (PC-12 cell treated with A-beta40) and memory impairment in ab in vivo Alzheimer's disease (AD) animal model induced with a continuous brain infusion of A-beta40. Effects on Dental Health A recent study has evaluated an array of plant foods with a potential activity on the development of microbial oral diseases. new data showing protective effects of mushrooms on betaamyloid peptide toxicity in the brain and mild cognitive impairment (both precursors to dementia) are very exciting and warrant further research on the ability of mushroom consumption to delay the onset of dementia / Alzheimer’s disease. Each of the LMM fractions tested prevented or reduced the induction of gene expression of the periodontal pathogens Prevotella 120 .3 Summary of Neurodegenerative Diseases / Cognition Although very preliminary.12. The fruiting body possessed stronger anti-oxidative and anti-inflammatory abilities for inhibiting neurocytotoxicity in A-beta40-treated PC-12 cells and A-beta40 accumulation in A-beta40-infused brain than mycelium. Hyper-phosphorylated tau (p-tau) protein expression.

1 Animal model (mouse) studies It has been demonstrated that dietary supplementation with white button mushrooms (Agaricus bisporus) enhances natural killer (NK) cell activity in C57BL/6 mice. P. The total bacterial numbers as well as numbers of eight key taxa in the oral environment were investigated over time. containing chlorhexidine. A study using isolated goat eye lens has reported that an extract of Pleurotus florida was able to prevent glucose-induced cataract in this in vitro model system (Aditya et al. 2009). The results indicated that Shiitake mushroom extract lowered the numbers of some pathogenic taxa without affecting the taxa associated with health. 2011). 15. in an artificial mouth model (constant depth film fermenter). Effects of Eye Health The efficacy of a Pleurotus ostreatus extract in preventing selenite-induced cataractogenesis has been evaluated. Effects on Immune Function 15. Agaricus bisporus has been shown to enhance maturation of bone marrow-derived dendritic cells of C57BL mice. a study has compared the effectiveness of Shiitake mushroom extract against the active component in a leading gingivitis mouthwash. Quinic acid from mushrooms has also been suggested to have anticaries activity (Gazzani et al. suggesting that increased intake of white button mushrooms may promote innate immunity against tumours and viruses through the enhancement of NK activity (Wu et al. simultaneous incubation of extract with selenite-challenged lenses caused a decrease in lens opacification by maintaining antioxidant components at near normal levels. Furthermore. unlike chlorhexidine which had a limited effect on all taxa (Ciric et al....intermedia and Actinomyces naeslundii. 2007a). In vivo.. suggesting that these LMM fractions could modulate the effects of bacteria associated with periodontal disease in gingival cells (Canesi et al. 2011).. 14.ostreatus prevented cataracts in 75% of rats (Isai et al. In vitro.. 2011). 2011). A functional assay for dendritic cell maturation showed that mushroom supplementation decreased cell endocytosis and increased intracellular 121 .

2009a).and COX-2-related disorders such as inflammation (Lee et al. 2008). APO inhibited both cyclooxygenase (COX)-1 and COX-2 enzyme activities with almost equal selectivity (Kohno et al. and the amount of TNF-alpha in PEC cultures. topical application of the polysaccharide resulted in marked inhibition of 12-O-tetradecanoylphorbol 13-acetate (TPA)-induced ear edema in mice. 2008b). Oral administration of FVE displayed antitumor activity through activating both innate and adaptive immunity of the host to prime a cytotoxic immune response and IFN-gamma played a key role in the anti-tumor efficacy of FVE (Chang et al.1 (BNL) hepatoma-bearing mice. These results suggest that this polysaccharide may be useful for the treatment of NO.. with the most marked increase on TNF-alpha level.5 µM) through reduced inducible NO synthase protein expression.. 2010) 122 .7 cells.. INF-gamma and IL-2 (Chang et al. Furthermore. Polysaccharides from Flammulina velutipes have also been shown to promote the metabolic activity of murine splenocytes and peritoneal exudate cells (PEC) and increase the amounts of TNF-alpha.. Flammulina velutipes polysaccharides may regulate murine immune function through promoting the production of TNF-alpha. Ganoderma lucidum (Leyss: Fr) Karst. A beta-glucan from Agrocybe chaxingu significantly inhibited lipopolysaccaride (LPS)induced nitric oxide (NO) and cyclooxygenase-2 (COX-2) expression levels in murine macrophage Raw 264. 2010b). Oral administration of 10mg/kg of an immunomodulatory protein (termed FVE) purified from Enoki mushroom (Flammulina velutipes) and known as an activator for human T lymphocytes. INF-gamma and IL-2 in the supernatants of splenocyte cultures. 50. 2-Amino-3H-phenoxazin-3-one (APO) from an extract of Agaricus bisporus IMBACH has been shown to inhibit NO production by mouse peritoneal macrophages in response to the pro-inflammatory stimuli lipopolysaccharide (LPS) and interferon (IFN)-gamma (LPS/IFN-gamma) at low concentrations (IC50=1. 2009a). 25 mg/kg) raised the serum levels of TNF-alpha and INF-gamma in Sarcoma-180 tumour-bearing mice. significantly increased the life span and inhibited the tumor size of BNL 1MEA.interleukin (IL)-12 levels suggesting an enhancement of both innate and T cell-mediated immunity leading to a more efficient surveillance and defence mechanism against microbial invasion and tumour development (Ren et al.. has also been shown to trigger immunomodulatory effects and reduce nitric oxide synthesis in Swiss male mice (Rubel et al. Flammulina velutipes polysaccharides (100..7R.

and enhancing leukocyte homing to atherosclerosis sites without affecting the lipoprotein profile (Goncalves et al. A. blazei enhanced local and systemic inflammation. dendritic cells and NK cells. upregulating pro-inflammatory molecules. To evaluate leukocyte homing and activation. blazei-induced transcriptional upregulation of molecules linked to macrophage activation (CD36. an experimental model of atherosclerosis.Oral administration of a protein from Flammulina velutipes has also been shown to possess anti-tumor activity in mice through activation of both innate and adaptive immunity of the host to prime a cytotoxic immune response with interferon-gamma having an effect on the anti-tumor efficacy of the protein (Chang et al. Analysis of the spleen showed higher levels of activation of neutrophils. such as interferongamma (IFN-γ). 2009b) 123 . Gandoderma lucidum extracts have also been shown to promote immune responses in normal BALB/c mice (Chang et al. NKT cells. 2010a). the effects of supplementation of mice with Agaricus blazei for 6 or 12 weeks has been studied on the activation of immune cells in the spleen and blood and on the development of atherosclerosis. and plaque vulnerability (MMP9) were seen after 12 weeks of supplementation. These cells attack cells infected with pathogens such as bacteria and viruses and produce cytokines.. A. blazei-supplemented animals. weight gain. which showed enhanced leukocyte migration to the spleen and heart of A. blazei has proatherogenic repercussions. leukocyte adhesion (VCAM-1)... Circulating NKT cells and monocytes were also more activated in the supplemented group. and glycemia were similar between the control and supplemented groups. The data show that the immunostimulatory effect of A. TLR4). Alpha-glucan-beta-glucan-protein complex polysaccharide from Agaricus blazei administered intraperitoneally or orally to Sarcoma 180 transplanted mice had no direct cytotoxic action on tumour cells in vitro. Using apolipoprotein E-deficient (ApoE(-/-)) mice. the polysaccharide showed a strong in vivo tumour growth-inhibitory effect suggesting that the effect of the polysaccharide is due to host-mediated mechanisms (Gonzaga et al. 2011).. and monocytes as well as increased production of TNF-alpha and IFN-gamma. Atherosclerotic lesion areas were larger in the aorta of supplemented mice and exhibited increased numbers of macrophages and neutrophils and a thinner fibrous cap. blood lipid profile. 2009a) and WEHI-3 leukemic BALB/c mice (Chang et al. which can modulate natural and specific immune responses. 2009). Food intake. There is growing evidence that such effects of a variety of mushrooms are mediated via promotion of natural immunity though macrophages. mice were injected with radiolabeled leukocytes.. However. neutrophil chemotaxy (CXCL1).

. and suppressed epithelial damage. prevented shortening of colon length and crypt length. the extract inhibited iNOS and TNF-alpha mRNA expression in colon tissue of DSS-induced colitis and in RAW264. This effect was related to the activation of NK cells indirectly through IL-12 produced by macrophages and dendritic cells (Kodama et al. 2010). and infiltration of inflammatory cells induced by DSS.. have been shown to elevate mouse natural killer (NK) cell cytotoxicity and stimulated macrophages to produce nitric oxide (Sarangi et al. Letinus edodes has been shown to have immunomodulating effects which are mediated via the enhancement of type-1 helper T cell-mediated cellular immunity (Hyun Ji et al. loss of crypts. The induction of granulocyte macrophage colony-stimulating factor (GM-CSF) production by water-soluble. 2006). Intake of Lentinula edodes mycelia extract significantly inhibited tumor growth in C57BL/6 mice inoculated with B16 melanoma. polysaccharide components of Ganoderma lucidum (Reishi) mycelia. 2011). Gray) has been shown to stimulate natural immunity in normal C3H/Hej mice. An extract of Cordyceps militaris has been shown to suppress dextran sodium sulphate (DSS)-induced acute colitis in mice and production of inflammatory mediators from macrophages and mast cells.. In Sarcoma-180-bearing mice.. gross bleedingand.. 2011). In addition. frondosa mixture to normal mice may enhance host innate immunity against foreign pathogens without eliciting an adverse inflammatory response (Wang et al.A polysaccharide extracted from the Maitake mushroom (Grifola frondosa S. 2011).7 cells.. Cordyceps militaris extract suppressed degranulation of mast cells in the colon of mice with DSS-induced colitis and in antigen-stimulated mast cells. A subsequent study from this group has suggested that the mechanism by which NK cells are activated is mediated through cytokines produced by antigen-presenting cells (Kodama et al.F. and this in vivo anti-tumor effect was not 124 . 2003). possibly providing an anti-inflammatory effect in a mouse model of colitis has also been reported (Hanaoka et al. 2008).. diarrhea. loss of goblet cells. A study has also suggested that oral administration of a submerged cultivated G. The extract significantly attenuated DSS-induced body weight loss. The data suggest that the extract from Cordyceps militaris has anti-inflammatory activity in DSS-induced acute colitis by down-regulating production and expression of inflammatory mediators (Han et al. proteoglycans from Pleurotus ostreatus mycelia.

When mice were fed with these micelles of beta-glucan (0. Phellinus linteus contains constituents that exhibit potent anti-tumour effects through activation of immune cells. 2009).. and increased the life span. has been reported to activate immune responses in cultured T-lymphocytes and macrophages. 2011). The concentrations of serum IL-2 only were significantly increased in Hepatoma 22 implanted mice using the same doses (Chen et al.. partly via the induction of cytokines (Cheung et al. 2010).. Oral administration of an endo-polysaccharide of Phellinus igniarius inhibited the growth of Sarcoma 180 and Hepatoma 22 cells that were implanted in mice. The Letinula edodes (Shiitake) mushroom-derived immuno-stimulant lentinan has also been reported to protect against murine malaria blood-stage infection by evoking adaptive immuneresponses (Zhou et al.. These effects also reportedly attenuated the severity of lupus in these mice (Chen et al.3-glucan (micellary mushroom extracts). 2007). the number of lymphocytes yielded by the small intestine increased by up to 40% and tumour cytotoxicity against P815 cells and cytokine production was also augmented. 2011b). 125 ... Serum IL-2 and IL-18 were significantly increased in the Sarcoma 180 implanted mice fed with the endo-polysaccharide at 500 mg/kg and 250 mg/kg compared with those in control. suggesting that smaller amounts of micellary beta-glucan might be useful for the potentiation of intestinal immunity (Shen et al. 2009).. possibly via a mitigation of T cell-mediated immunosuppression (Tanaka et al. Letinula edodes extracts have been dispersed with lecithin micelles to prepare superfine particles (0.2 microns in diameter) of beta-1.75mg/day/mouse. suggesting that the antitumor effect was mediated via enhancement of cell mediated immunity. 2005). A polysaccharide isolated from cultured Cordyceps sinensis (named cordysinocan).observed in nude mice.05 to 0. Cordyceps sinensis has also been shown to possess immuno-potentiating effects in lupus-prone autoimmune (NZB/NZW) mice via action on peripheral mononuclear T lymphocytes. smaller amounts of beta-glucan). Oral ingestion of Lentinula edodes extract restored immune responses of class I-restricted and melanomareactive CD8(+) T cells in these melanoma-bearing mice.linteus contain anti-allergic and immuno-potentiating properties (Inagaki et al. suggesting a T cell-dependent mechanism.. A recent study in mice has reported that boiling water soluble fractions from mycelium of P. Orally administered glucans from Pleurotus pulmonarius have also been recently reported to reduce acute inflammation in dextran sulfate sodium-induced experimental colitis in mice (Lavi et al. 2009).

A protein-bound polysaccharide extracted from Coriolus versicolor has been shown to have an immuno-potentiating effect.15. natural killer cell function. The enhanced activity of myeloperoxidase in the inflamed colonic segment was reduced by pleuran diets. The mechanism of the described protective effect of pleuran is not yet clear.6-branched 1..3-β-glucans which have been reported to inhibit tumour growth by stimulating of the immune system via effects on NK cells. a beta-glucan isolated from Pleurotus ostreatus. The effects of pleuran. Some of the more efficacious compounds have been reported to be 1. 2012). have been studied in a model of acute colitis in rats. being effective in restoring cyclophosphamide (CPA)induced immuno-suppression such as depressed lymphocyte proliferation. production of white blood cells and the growth of spleen and thymus in rats as well as in increasing both IgG and IL-2 production on which CPA did not have significant effects.3 In vitro studies (human cell lines) Numerous studies have described the effects of mushrooms and mushroom extracts on immune function with implications for inhibitory effects on tumour growth. Pleuran supplementation both in food and in drinking fluid significantly decreased the disposition to colitis. More 126 . The protein-bound polysaccharide partly restored CPA-induced immuno-suppression. 2001). 15. macrophages and via T cells and their cytokine production. but the authors suggest that the pleuran-enhanced antioxidant defence of the colonic wall against the inflammatory attack maybe a factor (Bobek et al. reflecting decreased neutrophil infiltration. The mechanism by which the protein-bound polysaccharide restored the immuno-suppression induced by CPA is unclear (Qian et al. The authors suggested that the protein-bound polysaccharide could be considered as a useful adjuvant. 1997). Pleuran was given either as a 2% food component or as 0..2 Animal model (rat) studies Agaricoglycerides of the fermented mushroom Grifola frondosa at the dose level of 500 mg/kg has been shown to possess anti-inflammatory and antinociceptive effects in preclinical animal models of inflammation and in some models of pain (Han and Cui. particularly combined with CPA or other chemotherapy in clinical treatment of cancer patients. Colitis was induced by intraluminal instillation of 4% acetic acid and after 48h the extent of colonic damage and several biochemical parameters were examined.44% pleuran hydrogel drink over 4 weeks.

. and tumor necrosis factor-alpha. but not CD4(+) T cells. Ganoderma lucidum also induced both nitric oxide and inducible nitric oxide synthase (iNOS). While considerable in vitro data have been generated. A polysaccharide (cordlan) isolated from Cordyceps militaris has also been shown to induce dendritic cell maturation through toll-like receptor 4 (TLR-4) signalling cascades (Hyung Sook et al. Polysaccharide krestin (PSK) is an extract from Trametes versicolor. IL-6.. which activate NF-kappa B and prompt the secretion of cytokines (Batbayar et al. and the activation of dendritic cells (DC) and T cells by PSK is dependent on TLR2. that has been shown to be a selective toll-like receptor TLR2 agonist (Lu et al.. 2009). Treatment with an inhibitor of nuclear factor-kappa B (NF-kappa B) reduced the induction of IL-1. Oral administration of PSK in neu transgenic mice significantly inhibited breast cancer growth. and TLR6 was increased by Ganoderma lucidum treatment. terpenes and furans have also been implicated in immune function. Innate immune cells are activated by the binding of beta-glucan to the dectin-1 receptor.. which was also potentiated by the presence of lipopolysaccharide. 2010). as have the health effects of beta-glucans in mushrooms (Rop et al.7 mouse macrophage cell secretion of several cytokines. 2008). The data indicate that PSK is a specific TLR2 agonist and has potent antitumor effects via stimulation of both innate and adaptive immune pathways (Lu et al. 2009. Ganoderma lucidum binds to dectin-1 and has been shown to induce RAW264. 2011b)... TLR4. and iNOS in a concentration-dependent manner and expression of toll-like receptor (TLR)2. interleukin (IL)-6.recent work has implicated polysaccharides with varying sugars and some are α. including granulocyte colony-stimulating factor.. mushroom proteins. in vivo studies are few and the small number of clinical studies that have been carried out have have often been poorly controlled and with small numbers of patients.. 2011). likely by binding to dectin-1 and toll-like TLR-2/6 receptors. The immunobiology of mushrooms has been reviewed (Borchers et al. Components of PSK have also been reported to act as ligands for TLR4 receptors 127 . 2011). 2011a). The result indicates that Ganoderma lucidum induces macrophage secretion of inflammatory cytokines. Furthermore. tissue inhibitor of metalloproteinase-1.rather than β-glucans. Rondanelli et al. PSK did not inhibit tumor growth in TLR2(-/-) mice suggesting that the antitumor effect is mediated by TLR2. An Agaricus brasiliensis-derived cold water extract has also been reported to have some water-soluble toll-like receptor ligand complexes and induce cytokine production via a tolllike receptor 2-dependent mechanism (Yamanaka et al. with the antitumor effect of PSK being dependent on both CD8(+) T cell and NK cells. regulated upon activation normal T cell expressed and secreted (RANTES).

bisporus polysaccharides was mediated in part through activation of nuclear factor-kappaB. prostate. cibarius and L. when murine Sarcoma 180 cells exposed to ABP-1 or ABP2 were implanted subcutaneously into mice. Beta-glucan-rich polysaccharide extracts from Agaricus bisporus (but not A.. Lentinan. 2011). C. Coprinus comatus. A further study from the same group has subsequently also shown that alkali-soluble proteoglycans 128 . 2011a). Cantherellus cibarius. a cell wall beta-glucan from the fruiting bodies of Lentinus edodes has been reported to exert its immunomodulating activity (in RAW 264... 2012).7 macrophages) by activation of MAPK signaling pathways without secretion of TNF-alpha and NO (Xu et al. Sang Chul et al. Both ABP-1 and ABP-2 had the ability to inhibit the growth of human breast cancer MCF-7 cells but had little effect on the growth of human colon. interleukin-6. and murine Sarcoma 180 cells. 2010a). However.. or spores of Ganoderma lucidum) stimulated nitric oxide production by bone marrow-derived macrophages.deliciosus exhibited the higher anti-inflammatory activities inducing inhibition of NO production and iNOS. Cratarelluscornucopioides. blazei Murill. bisporus.7macrophages. and tumor necrosis factor-alpha. PSK has also been reported to reduce toxicity of current treatments used in patients with metastatic colorectal cancer (Shibata et al. Two polysaccharide fractions (designated as ABP-1 and ABP-2) isolated from Agaricus bisporus have been shown to stimulate the production of nitric oxide... IL-1beta and IL6 mRNAs expression in response to LPS stimulation (Moro et al. Methanol extracts from Agaricus bisporus. 2012). suggesting their potential immunomodulating activities (Bao and You.. The effects of PSK in cancer therapy and the possible mechanism of action have recently been reviewed (Sun et al. These data provide evidence that macrophages possibly contribute to the antitumorigenic effects of Agaricus bisporus polysaccharides (Jeong et al. 2010). gastric cancer. 2012. Boletus edulis. Lactarius deliciosus and Pleurotus ostreatus have shown antiinflammatory activity in LPS activated RAW 264.7 cancer cells to release nitric oxide and prostaglandin E2. Phellinus linteus. 2012). a reduction in tumor growth was observed compared with that observed in control mice. It has been suggested that branching of the betaglucan chain is essential for immune-stimulating activity (Volman et al. 2011).. A. Water-soluble extracts isolated from Hypsizigus marmoreus have been shown to significantly stimulate Raw 264.leading to induction of TNF-alpha and IL-6 inflammatory cytokines (Price et al. Modulation of macrophage function by A.

Enhaced proliferation of bone marrow macrophages in adose-dependent manner by Lingzhi or Reishi medicinal mushroom Ganoderma lucidum immunomodulating substance (GLIS) has been demonstated. The results showed that PCP-3A failed to affect RAW 264.7 viability at a concentration up to 6. which have recently been summarised in a minireview (Cheung et al. prostaglandin E2 as well as cytokines.. and suppressed antigen-induced signal protein phosphorylation of Lyn. including iNOS and NF-kappaB (Chen et al. indicating that GLIS activates the immune system by modulating cytokine production (Ji et al. 2011. Pleurotus citrinopileatus. 2011). induction of cellular respiratory burst activity. Zhe et al. and IL-12 secretion. eryngii may provide some insights into the mechanisms for the possible prevention and treatment of allergic and inflammatory responses (Eun Hee et al. IL-12p35. 2012). The anti-allergenic potential of Pleurotus eryngii extract (PEE) in antigen-stimulated RBL2H3 mast cells has been evaluated with PEE inhibiting allergy markers. PEE also suppressed the expression and production of interleukin-4 and reduced antigen-induced NFAT and NF-kappaB transcriptional activity in antigen-sensitized mast cells. and increased levels of IL-1 beta. and the production of NO and PGE2 in lipopolysaccharideactivated macrophages via the down-regulation of certain pro-inflammatory mediators. The data indicate that this extract from P. PKC.7 cells. Another study in Raw 264. 2011).7 cells to release nitric oxide. IL-18.. IL-12p40. IL-6. such as IL-1 beta. PEE also decreased the levels of proinflammatory cytokines and COX-2 and iNOS expression in antigen-sensitized mast cells.. 129 . PLCgamma2. Exposure of bone marrow macrophages to GLIS resulted in significant increases in NO production. and TNF-alpha gene expression and levels of TNF-alpha. IL-1 beta. TNF-alpha and IL-6 by inducing mRNA expression (Bao et al.. Akt. 2011a). 2011).and acid-soluble proteoglycans from Hypsizygus marmoreus significantly stimulated Raw264. in antigen-sensitized RBL-2H3 cells.. including release of hexosaminidase and histamine. Polysaccharides isolated from the fruit bodies and mycelia of both medicinal and edible mushrooms have been found to exert immunomodulatory function and antitumor activity in numerous in vivo and in vitro studies.. and MAP kinases.25 g/mL. but inhibited lipopolysaccharide (1 g/mL)-induced expression. has evaluated anti-inflammatory effects of a bioactive nonlectin glycoprotein (PCP-3A) isolated from the fresh fruiting body of the golden oyster mushroom.

Cordlan polysaccharide from the mushroom Cordyceps militaris has been shown to induce dendritic cell maturation through toll-like receptor 4 (TLR4) signaling pathways (Kim et al.. Dedritic cells pulsed with colon-26 tumor lysate in the presence of the mushroom polysacchardide induced both therapeutic and preventative effects on colon-26 tumor development in BALB/c mice (Masuda et al.. Beta glucan from Grifola frondosa (Maitake) has recently been shown to enhance umbilical cord blood stem cell transplantation (from full-term infants) in the nonobese diabetic/severe combined immunodeficient (NOD/SCID) mouse. and to stimulated G-CSF production. 2011). However.human committed hematopoietic progenitor (HPC) cells compared to the conventional stem cell culture medium... 2011).3-beta-D-glucan has been suggested to activate dendritic cells via Mitogen Activated Protein Kinase (MAPK) and NF-kappaB signaling pathways. supporting its immunotherapeutic potential (Masuda et al. A further study from the same group has demonstrated that a soluble beta-(1.. While granulocyte colony stimulating factor (G-CSF) treatment following chemotherapy is effective in treating against bone marrow myelotoxicity. The study showed that oral MBG promoted maturation of HPC to become functionally active myeloid cells and enhanced peripheral blood leukocyte recovery after chemotoxic bone marrow injury (Lin et al. 2010). Oral administration of MBG to recipient NOS/SCID mice led to enhanced homing at 3 days and engraftment at 6 days 130 . 2010a). which are signaling intermediates downstream of TLR4 (Kim et al. The Maitake beta glucan (MBG) enhanced mouse bone marrow (BMC) and human umbilical cord blood (CB) cell granulocyte-monocyte colony forming unit (GM-CFU) activity in vitro and protected GMCFU forming stem cells from doxorubicin (DOX) toxicity. 2010b).3) (1. some immunomodulatory effects of mushrooms do not necessarily depend on beta-glucan (Lee et al. High 6-branched 1. A polysaccharide extracted from Grifola frondosa has been shown to induce cell-mediated immunity by inducing bone marrow dendritic cell maturation and an antigen-specific Th1 response by enhancing dendritic cell-produced IL-12. MBG promoted a greater expansion of CD34+CD33+CD38.. 2010b).6)-glucan obtained from Grifola frondosa induced cell proliferation and cytokine production without excessive inflammation in macrophages. a beta-glucan extract from the Maitake mushroom Grifola frondosa (MBG) has been shown to enhance colony forming unit-granulocyte monocyte (CFU-GM) activity of mouse bone marrow and human hematopoietic progenitor cells (HPC).

These immunomodulatory effects were shown to be mediated via NF-kappaB and Mitogen Activated Protein Kinase (MAPK) pathways. lucidum have been shown to contain immunomodulating activity by acting directly on human peripheral blood mononuclear cells and thereby modulating T cell activation (Jeurink et al. 2002). Agaricus blazei Murill has been reported to possess biological effects that include immunomodulatory activities.. These results suggest that this fraction establishes Th-1 dominance which induces cellular immunity in the population that was Th-2 dominant due to carcinoma (Inoue et al.in mouse bone marrow compared to control mice. 2008). 2007). splenocyte proliferation rate. 2009b).. preferring a Th1 response. The fraction decreased the activation of B cells and potentiated the activation of helper T cells. Ganoderma lucidum mycelia did not potentiate nitric oxide production in RAW264. More CD34+ human cord blood cells were also retrieved from mouse spleen in beta glucan treated mice at 6 days after transplantation. delayed-type hypersensitivity.. Interferon-gamma release from human whole blood was also enhanced after 3 days of culture with Ganoderma lucidum mycelia. 2006). A protein from Ganoderma lucidum has also been shown to effectively promote the activation and maturation of immature human monocyte-derived dendritic cells. and IL-18 by whole spleen cells and lymph node cells. interleukin (IL)-12 p70... A polysaccharide purified from Ganoderma lucidum has also been shown to induce gene expression changes in human dendritic cells and promote T helper 1 immune response in BALB/c mice (Lin et al.7 cells (Kuo et al.. The protein extracts of V. 2006). resulting in enhanced cellular immunity. A beta-glucan extracted from the fruiting body of the Maitake mushroom (Grifola frondosa) has been reported to activate cellular immunity and expresses anti-tumour effects. It also induced the production of interferon (IFN)-gamma. with the anti-tumour effects relating to its control of the balance between T lymphocyte subsets Th-1 and Th-2. but suppressed that of IL-4. In whole blood. 2009a). such as stimulation of serum immunoglobulin G level. Ganoderma lucidum mycelia have been reported to stimulate tumour necrosis factor-alpha (TNF-alpha) and IL (interleukin)-6 production after 8h of treatment. suggesting that the protein may possess a potential effect in regulating immune responses (Lin et al. The studies suggest that Maitake beta glucan promoted hematopoiesis through effects on CD34+ progenitor cell expansion ex vivo and when given to the transplant recipient could enhance CD34+ precursor cell homing and support engraftment (Lin et al. and tumour necrosis factoralpha secretion by splenocytes (Chan et al. However. volvacea and G. Agaricus blazei has also been 131 ..

while treatment with pH 2 and pH 13 buffers only resulted in an insignificant decrease of the induced TNF-a and NO production. COX-1 and -2 (Diyabalanage et al.. These data show thermal/freezingresistance..7 macrophage cells. in their stimulations of TNF-α production.. 2007b).. Naematoloma sublateritium. Possible immuno-modulating effects of Ganoderma lucidum mycelium extract (GL-M) and spore extracts on human immune cells have been studied. with 96. and P.. determined by the induction of TNF-α and NO production by RAW264. Ceramide from Agrocybe aegerita has also been reported to inhibit the cyclooxygenase enzymes.7 cells in vitro. Phellinus linteus butanol fractions (PLBF) inhibit the production of NO and PGE2 through the down-regulation of inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2) gene expression via reactive oxygen species (ROS)-based NF-kappa B and mitogen-activated protein kinase (MAPK) activation suggesting a potential effect on inflammation-associated disorders (Kim et al. 24 h) treatments did not reduce the effects of Agaricus bisporus lectin (ABL) and the immunomodulatory protein of Auricularia polytricha on macrophage-activating functionalities. acid/alkali tolerance and dehydration stable properties of the extracts tested with respect to their effects as immune stimulants (Chang et al. An extract of Agaricus blazei Murill has also been reported to differentially stimulate production of pro-inflammatory cytokines in human monocytes and human vein endothelial cells in vitro (Bernardshaw et al.6% of activities being retained. infection and cancer have been reviewed (Hetland et al. 2005a).reported to have inhibitory effects on mast cell-mediated anaphylaxis-like reactions (Choi et al.5% and 84. The immunomodulatory effects of mushrooms appear to be unaffected by food processing procedures. Ethyl acetate extracts of Ganoderma applanata... salmoneostramineus have been shown to have in vitro anti-inflammatory activity via cyclooxygenase-2 inhibitory effects compared to COX-1 inhibition. 2008). In RAW 264. 30 min) and freezing (-80°C. The effects of Agaricus blazei Murill on immunity. The differential effect of GL-M and GL spore extract (GL-S) on proliferation and Th1/Th2 cytokine mRNA expression of human peripheral blood mononuclear cells 132 . Boiling (100°C. while ethyl acetate extracts of Agrocybe cylindracea exhibited high inhibition of the COX-2 enzyme (Elgorashi et al.. Pleurotus eryngii. 2007)(Kim et al. 2007). respectively. Agaricus bisporus lectin (ABL) and Auricularia polytricha also withstood vacuum dehydration. Furthermore. Dendritic cells (DCs) are antigen-presenting cells and their role in DC-based tumour vaccines has been well defined. 2008). 2006). 2006b) and up-regulate genes such as the interleukins IL1B and IL8 (Ellertsen et al. 2008).

2005). The complete amino acid sequence of FIP-fve was determined by protein sequencing techniques. GL-M enhanced maturation of DCs in terms of upregulation of CD40. half-cystine and histidine residues. CD80. brasiliensis. Ganoderma lucidum can biotransform 20%-30% of 133 .. Ganoderma lucidum has also been shown to enhance the expression of CD40 and CD80 molecules on human peripheral blood monocytic cells derived from both sexes in a dose-dependent manner (Ahmadi and Riazipour.(PBMCs) and monocytes has been evaluated. 2008). 2006) with the effects being proportional to surface area. a more efficient way of increasing the vitamin D2 content is to irradiate sliced mushrooms (Ko et al. but GL-M was a relatively stronger Th1 stimulator. In contrast to GL-S. Both extracts stimulated Th1 and Th2 cytokine mRNA expression. FIP-fve consisted of 114 amino acid residues with an acetylated amino end. Interestingly. whereas GL-S showed a mild suppressive effect. An immunomodulatory protein (FIP-fve) has been isolated and purified from Flammulina velutipes. 1995). FIP-fve was able to hemagglutinate human red blood cells. Mushrooms are a good source of vitamin D and studies have reported that sunlight-activated biosynthesis of vitamin D from ergosterols within mushrooms (fresh and dried) can increase vitamin D levels considerably. The effects on the phenotypic and functional maturation of human monocyte-derived DCs were also investigated. Vitamin D is an important factor for immune function.. A. and its suppression of systemic anaphylaxis reactions and local swelling of mouse footpads. The data provide evidence that GL-M has immunomodulating effects on human immune cells and may be of use as a natural adjuvant for cancer immunotherapy with dendritic cells (Chan et al. 2009). 2008). The immunomodulatory activity of FIP-fve was demonstrated by its stimulatory activity toward human peripheral blood lymphocytes. FIP-fve was found to enhance the transcriptional expression of interleukin-2 and interferon-gamma (Ko et al. and lacked methionine. and CD86. 2005). e. which has significant implications in the context of health (Stamets. and G. GL-M induced the proliferation of PBMCs and monocytes. GL-M-treated DCs only modestly enhanced lymphocyte proliferation in allogenic mixed lymphocyte culture with mild enhancement in Th development... lucidum strongly generated reactive oxygen species (suggesting immunomodulatory effects) in human PBMCs and K 562 cells in vitro (Wei et al. bisporus.g. and also reduced fluorescein isothiocyanate-dextran endocytosis. Phenolic compounds present in mushroom extracts from A. Vitamin D2 levels can also be significantly increased by irradiation of mushrooms with ultraviolet light (Jasinghe and Perera.

in vivo studies are few and the small number of clinical studies that have been carried out have often been poorly controlled and with small numbers of patients.3-β-glucans which have been reported to inhibit tumour growth by stimulating of the immune system via effects on natural killer (NK) cells. 2008). macrophages and via T cells and their cytokine production.rather than β-glucans. although structure–function relationships have been described between anti-tumor activities and structural characteristics of β-D-glucans. There was less fat accumulation in the livers of mice on the mushroom diet.inorganic Se from substrate with Se being biotransformed preferentially in forms of Secontaining proteins. 15. but have been shown to enhance host-mediated immunomodulatory responses. Genes related to 134 .6-branched 1. Effects on Liver Health Dietary intake of white button mushroom. mushroom proteins.4 Summary of Immune Function Numerous studies have described the effects of mushrooms and mushroom extracts on immune function with implications for inhibitory effects on tumour growth. These mushroom polysaccharides generally do not exert cytotoxic effects on tumor cells.. 16. and the mice had improved glucose clearance ability. Furthermore. lucidum appear to be synergistic (Du et al. terpenes and furans have also been implicated in immune function. While considerable in vitro data have been generated. More recent work has implicated polysaccharides with varying sugars and some are α. The mechanisms by which these polysaccharides exert their immunomodulatory effects are not entirely clear. Some of the more efficacious compounds have been reported to be 1. The immune-regulatory activities of both Se and proteins from G. They have been demonstrated to have thermal/freezing resistance. Agaricus Bisporus has been shown to significantly lower liver weight and hepatic injury markers in ovariectomized mice (a model of postmenopausal women). Mushroom lectins have been reported to be immuno-modulatory proteins. acid/alkali tolerance and dehydration stable properties suggesting that they would be stable during food processing applications and therefore suitable for functional food/health utilization.

vitamin D2 and/or calcium derived from irradiated Lentinula edodes may improve bone mineralization directly and by inducing the expression of calcium-absorbing genes in the duodenum and kidney (Lee et al. particularly the genes for fatty acid synthetase (Fas) and fatty acid elongase 6 ( Elovl6).. A study in 4-week old mice fed low calcium and a vitamin D deficient diet showed significantly increased femur density and tibia thickness in mice fed calcium plus vitamin D2-enhanced mushrooms.. A recent randomized controlled trial has also demonstrated that the bioavailability of vitamin D2 from vitamin D2-enhanced mushrooms via UV-B irradiation improved vitamin D status in humans to a level similar to that of a vitamin D2 supplement (Urbain et al.1 Animal model studies Ethanol extracts of Ganoderma lucidum have been evaluated against ovariectomized (Ovx)-induced deterioration of bone density in 11-week-old female Sprague Dawley (SD) rats (Miyamoto et al. 2009b). 17.the fatty acid biosynthesis pathway. and the secretion of osteoprotegerin from the 135 . In vitro mechanistic studies using the HepG2 cell line showed that down-regulation of the expression of FAS and ELOVL6 by this mushroom extract was through inhibition of liver X receptor (LXR) signalling and its downstream transcriptional factor SREBP1c (Kanaya et al. The results indicated that in mice. Effects on Osteoporosis / Bone Mineral Density 17. Lentinula edodes that are exposed to UV radiation contain enhanced vitamin D2 and have a much higher calcium content than non-irradiated mushrooms. PEX also increased the expression of the Runx2 gene. 2011). 2009) with the treated rats showing improved bone density.2 In vitro studies (human cell lines) The effects of Pleurotus eryngii extracts (PEX) on bone metabolism have been studied. were down-regulated in the liver of mushroom-fed mice. 2011b). and the expression of duodenal and renal calcium transport genes was significantly induced... PEX treatment showed an increase in the alkaline phosphatase activity of the osteoblasts and in the osteocalcin mRNA expression from primary osteoblasts. 17.

. In another osteoblastic cell line (SaOS-2) cells incubated with Grifola frondosa for 21 days. and by inducing the expression of calcium-absorbing genes in the duodenum and kidney. Two sterols isolated from the edible mushroom Leccinum extremiorientale have been shown to suppress the formation of osteoclasts and thereby may have some value in the treatment of osteoporosis (Choi et al. showed a nearly 2-fold higher mineralization than cells cultured with a positive control.osteoblasts showed marked increases after treatment with PEX. significantly increased lipid-peroxide levels in the plasma of adjuvant-induced arthritic rats. 2006b). 2010). 2007). 2006).. 17. Osteoclast forming suppressive compounds have been isolated from the mushroom Agrocybe chaxingu (Abel et al. Effects on Rheumatoid Arthritis 18.. demonstrating the activity of Grifola frondosa extract as a bone-inducing agent (Saif et al.. 18. In vivo studies.1 Animal model studies A polysaccharide–protein complex. using rats with ovariectomy-induced osteoporosis revealed that PEX alleviated the decrease in the trabecular bone mineral density (Kim et al. without having a substantial effect on the uterus (Shimizu et al.). 2007).. isolated from Phellinus rimosus (Berk.3 Summary of Osteoporosis/Bone Mineral Density In vitro studies have reported positive effects of mushroom extracts on mineralisation of osteoblastic cell lines. Animal studies have reported increased bone density following consumption of mushroom extracts. while mice fed calcium plus vitamin D2-enhanced (UV irradiated) mushrooms showed improved bone mineralization through a direct effect on the bone. An ethanol extract of Pleurotus eryngii has also been reported to help protect against bone loss caused by estrogen deficiency. The cultivation of human osteosarcoma cells HOS58 in the presence of an aqueous extract of Grifola frondosa resulted in a significant elevation of alkaline phosphatase activity of the cells in comparison to untreated cells. It has been suggested that the mechanisms for these effects is an increasein the alkaline phosphatase activity of osteoblasts. The antioxidant 136 .

1). 2009). but 15 days post withdrawal of SM. (Aphyllophoromycetideae) has been shown to accelerate wound healing in rats (measured as less scar width at wound enclosure with the healed wound containing fewer macrophages and more collagen with angiogenesis. only SM increased plasma IL-6 by 1. Although both types of mushrooms reduced plasma TNF alpha (34%. The effects of white button mushrooms (WBM) and shiitake mushrooms (SM) on collageninduced arthritis (CIA) have been studied in 8-wk-old female dilute brown non-agouti mice.15 +/. This effect of SM was not seen with WBM consumption (Chandra et al.82 to 3.3-fold (P < 0. Whereas 58% of control mice had a CIA index 7.) pers.. only 23% of WBM and 29% of SM mice did (P = 0. Anti-arthritic activity of a beta-(1.05) (Chandra et al. 19. 2011).11 +/0.6)-D-glucan from Pleurotus ostreatus has been reported (Bauerova et al. Hericium erinaceus (Bull. While these data provide some suggested benefits in this animal model. and reduced blood glutathione was decreased. an aqueous extract of the culinary-medicinal lion's mane mushroom.0..: Fr. 2011a). WBM. SM). Compared to the control diet. WBM and SM tended to reduce the CIA index from 5. 2009. 6-9 to 1-2) 31 d post-collagen injection. 137 . Treatments with various concentrations of the polysaccharide–protein complex modulated the alterations produced in arthritic animals in a dose-dependent manner (Meera et al. It should be noted however. and further studies are needed to confirm such effects.95 (P = 0. compared to wounds dressed with sterilized distilled H2O (Abdulla et al.1 Animal model studies In Sprague Dawley rats. 2011b). statistical validation of these data is borderline. 64%. liver histology was completely normalized.3/1. that another study has suggested that supplementing a mouse diet with 5% SM can result in a fatty liver (an elevation in IL-6 is also implicated in fatty liver disease).. 2011) in a rat model which involved an immunomodulating effect on cytokine plasma levels that changed markedly with arthritis progression..06) (median.. Effects on Wound Healing 19.enzymes superoxide dismutase and glutathione peroxidase were elevated in adjuvant-induced rats.. Rovensky et al.

mucosal interleukin-2 (IL-2) and TNF-α in rats with oral ulceration. 2008)... 90%.. and 72 hours of treatment was 82%. A study has been undertaken to determine whether it might have inhibitory activity on Tenon's capsule fibroblasts in in vitro models of wound healing and therefore have a use in the modification of scar formation after glaucoma surgery. and 100%.. 2004). (Aphyllophoromycetideae) has also been shown to reduce ulceration in ethanol-induced gastric ulcers in rats (Mahmood et al. respectively.. Polysaccharide fractions from Ganoderma lucidum have also been shown to have an active component with healing efficacy on acetic acid-induced ulcers in the rat. which may represent a useful preparation for studies on the prevention and treatment of peptic ulcers (Gao et al. An ethanol extract of Ganoderma lucidum (Fr. The IL-1 beta level in the serum and the NF-kappa B level in the tissues indicate that the healing potential was associated with attenuation of proinflammatory cytokines (Omar et al. 19. Oral feeding of Lentinus squarrosulus extract (250 mg/kg) offered significant gastric mucosal protection of Sprague-Dawley rats compared to cimetidine (50 mg/kg). Agaricus bisporus 138 . via a mechanism that may involve an increase in the migration of macrophages and fibroblasts. Karst.) P.2 In vitro studies (human cell lines) The edible mushroom lectin from Agaricus bisporus has been reported to have antiproliferative effects on a range of cell types. 2009c).Impaired wound healing in diabetes mellitus is a major clinical problem. at oral doses of 500 mg/kg and 1000 mg/kg has also been shown to attenuate Indomethacin-induced gastric ulceration in rats (Rony et al. 48. The ulcer healing rate of ulcerated rats after 24. 2009).: Fr. Pretreatment with Hericium erinaceus (Bull. suggesting that Lentinus edodes polysaccharide may play a part in ameliorating oral ulceration (Yu et al. 2011). Wound closure in streptozotocin-induced diabetic rats has been shown to be significantly accelerated by oral administration of Sparassis crispa (SC) a mushroom with a β-glucan content of more than 40%. 2011).) Pers. Human ocular fibroblasts in monolayers and in three-dimensional collagen lattices were exposed to Agaricus bisporus (0-100 µg/ml). Administration of Lentinus edodes polysaccharide significantly raised activities of serum antioxidant enzymes and decreased levels of serum.. with beta-glucan from SC directly increasing the synthesis of type I collagen (Kwon et al.

MMP-1) expression in UVA-irradiated HDF without any significant cytotoxicity. while Hericium erinaceus (Bull. 2009c) have demonstrated efficacy in treatment of ulceration in rats via mechanisms which involved raised activities of serum antioxidant enzymes and decreased levels of serum... frondosa HB0071 may contribute to an inhibitory action in photo-ageing skin by reducing the MMP 1-related matrix degradation system (Bae et al.) Pers. The data showed that Agaricus bisporus possesses key features required of an agent that might control scarring processes and suggest that Agaricus bisporus may be especially useful where subtle modification of healing may be needed although further studies are required (Batterbury et al.1 In vitro studies (human cell lines) The photo-protective potential of exoploysaccharides (EPS) from Grifola frondosa HB0071 has been tested in human dermal fibroblasts (HDF) exposed to ultraviolet-A (UVA) light. Protective Effects Against UV-Light 20.. The anti-mutagenic effect of the mushrooms Lentinula edodes and Agaricus blazei have been studied on conidia of Aspergillus nidulans when exposed to short wave ultraviolet (UV) light.. 2009c). It was reported that EPS had an inhibitory effect on human interstitial collagenase (matrix metalloproteinase.. The data demonstrated a radio-protective and anti-mutagenic effect of L. The data suggested that EPS obtained from a mycelial culture of G. (Aphyllophoromycetideae) (Mahmood et al. 2002). A dose-dependent inhibition of proliferation and lattice contraction without significant toxicity in an in vitro model of wound healing (human ocular fibroblasts in monolayers and in three-dimensional collagen lattices) by Agaricus bisporus (0-100 mg/ml) has been shown (Batterbury et al.. and polysaccharide fractions from both Ganoderma lucidum (Gao et al. 2002). 2005). 139 . 20. mucosal interleukin-2 (IL-2) and TNF-α (Yu et al. The treatment of UVA-irradiated HDF with EPS resulted in a dose-dependent decrease in the expression level of MMP-1 mRNA.caused a dose-dependent inhibition of proliferation and lattice contraction without significant toxicity.: Fr. 2004) and Lentinus edodes (Yu et al.. 2008).

. 140 . Bronchoscopies were effective in removing the mucous plugs and relieving the patient's symptoms (Amitani et al. 2004). liner atelectasis. slight ground glass opacities. Pulmonary function tests showed a mild restrictive pattern. 2002).e.. pulmonarius can induce delayed-type reactions consistent with an acute eczema in atopic individuals. and reticulo-nodular shadows on chest CT. commune. 1996). A study has shown that spores of the oyster mushroom P. Chest CT scan revealed reticulo-nodular shadows. weight loss. Serum precipitins to the Shiitake mushroom spores were positive.. once exposure was eliminated. and "gloved finger" shadows on a chest roentgenogram. Low trehalase activity in a small number of patients has been reported to be associated with abdominal symptoms caused by edible mushrooms. A case of mucoid impaction of the bronchi due to a hypersensitivity reaction to the monokaryotic mycelium of Schizophyllum commune has been reported. cough. Trehalose maldigestion can cause symptoms similar to those of lactose maldigestion and intolerance (Arola et al. are airborne components and established as causes of respiratory allergies. peripheral eosinophilia.. Hypersensitivity to Mushrooms in Humans A recent individual case study has reported hypersensitivity pneumonitis induced by Shiitake mushroom spores in a worker involved in mushroom production (Ampere et al. persistent cough. bilateral fine crackles. The diagnosis of hypersensitivity pneumonitis due to inhalation of Shiitake mushroom spores was established as a result of the improvement of all of the clinical symptoms of the patient. Spores of Pleurotus pulmonarius. The patient was hospitalized because of mild asthma attacks. mild restrictive pattern of pulmonary function. 21.. Cultures of the mucous plugs and sputum samples yielded white.. 2012). i. particularly in those with atopic dermatitis (Fischer et al. blazei mushrooms on eukaryotic cells when exposed to UV radiation (Souza-Paccola et al. a species of Oyster mushroom. felt-like mycelial colonies that were later identified as the monokaryotic mycelium of S.edodes and A. and subpleural opacities in both lung fields.

and it has been suggested that this dermatitis may be photosensitive as nearly half of the patients studied developed the dermatitis on skin exposed to sunlight (Hanada and Hashimoto. and increased gastrointestinal symptoms (Levy et al. The lymphocyte count in the bronchoalveolar lavage fluid was increased. 1991). Chest computed tomography demonstrated centrilobular nodules and increased attenuation in both lungs. on his return to work.. 1998). primarily in Japan. Hypersensitivity pneumonitis induced by Pleurotus eryngii spores has been reported in a worker in an Eringi (Pleurotus eryngii) mushroom factory who had worked there for 6 years. A study has been conducted with 10 people where each participant ingested 4g of Shiitake powder daily for 10 weeks (trial 1). Precipitins against the 141 . Shiitake dermatitis after the ingestion of raw Shiitake mushrooms has been reported. A recent study has also described a mushroom intolerance in some patients with Crohn’s disease (Petermann et al. A diagnosis of contact urticaria and allergic contact dermatitis from Shiitake mushrooms was confirmed by prick and patch tests. increased eosinophil granule proteins in serum and stool.1999). Symptoms and eosinophilia resolved after discontinuing Shiitake ingestion. and transbronchial lung biopsy specimens showed lymphocyte alveolitis with epithelioid cell granulomas in the alveolar spaces. After admission. fever and hypoxemia appeared again. and the protocol was repeated in the same subjects after 3 to 6 months (trial 2). cases with Shiitake dermatitis occurred after eating boiled or cooked Shiitake mushrooms suggesting that a non-thermolabile factor/component may be involved (Ha et al. 2003).. The lymphocyte stimulating test was positive against extracts of Eringi spores. However. 1998). the patient's symptoms improved rapidly without medication. The respiratory symptoms. The authors reported that daily ingestion of Shiitake mushroom powder in five of 10 healthy persons provoked blood eosinophilia. Chest radiography showed diffuse fine nodular shadows.. Skin and respiratory symptoms developed within 2 months of exposure in a patient involved in the commercial production of Shiitake mushrooms.. but contrary to the previous reports in Japan. the presence of precipitating IgG antibodies to Shiitake spores and increased amounts of inflammatory cells and T lymphocytes in bronchoalveolar lavage indicated allergic alveolitis (mushroom worker's disease) (Tarvainen et al. 2009). Gastrointestinal symptoms coincided with eosinophilia in two subjects. The patient suffered from hypoxemia while breathing room air. their timing. A study in Korea has also reported dermatitis effects.

An evaluation of protective measures concluded that complete cessation was the best treatment for hypersensitivity pneumonitis. In Japan. surfactant protein-D (SP-D) concentration and severe ground-glass opacity on chest high-resolution computed tomography. 142 . The use of a mask was ineffective for patients with a high serum Krebs von der Lungen-6 (KL-6). 2003). The symptoms appear to improve rapidly without medication (Miyazaki et al.. more than 30 cases of HP induced by mushroom spores have been reported and therefore this is an occupational health and safety issue.. 2006).. 2004)... although separation from the antigen along with corticosteroid therapy.extracts of Eringi spores were detected by the double immunodiffusion test. while avoidance of the antigen is important (Kai et al. and hypersensitivity pneumonitis to spores of Pholiota nameko has been reported in a mushroom farmer. Initial treatment with oral prednisolone was recommended for patients with high levels of total cell counts in bronchoalveolar lavage fluid (Tsushima et al. Treatment with steroids seems to have a limited effect. Hypersensitivity pneumonitis in a mushroom industry worker due to Pholiota nameko spores has been reported (Nakazawa and Tochigi. 1989). beclomethasone dipropionate (BDP) dissolved in hydrofluoroalkane-134a (HFA)(Tanaka et al. 1996). Bunashimeji-related hypersensitivity pneumonitis has been reported in workers who cultivate this mushroom in indoor facilities. The diagnosis was hypersensitivity pneumonitis (HP) caused by Eringi spores. 2008). Chronic hypersensitivity pneumonitis induced by Lentinula edodes (Shiitake) mushrooms in long-term mushroom industry workers appears to be characterised by a tendency toward increasing lymphocytes and high CD4/CD8 ratio in bronchoalveolar lavage fluids. resulted in the symptoms and inflammatory effects quickly subsiding (Inage et al. Occupational hypersensitivity pneumonitis (HP) caused by Grifola frondosa (Maitake) mushroom spore has been successfully treated with an extra-fine aerosol corticosteroid. related to air quality in mushroom factories that needs to be addressed.

when the affected person is removed from the factory environment. respectively). Cancer survivors took 1.4 g ABM granulated powder per day orally for 6 months. The intake of beta-glucan resulting from the proposed use is low compared to the intake estimated from the 143 . none of the adverse events occurred in a dose-dependent manner.8. However. Seventy-eight patients were assessed for safety of ABM (30/24/24 subjects at 1/2/3 packs per day. The small number of cases reported. free glucose and Ncontaining constituents). usually involve workers in the commercial production of mushrooms. primarily in Japan. The study showed that ABM does not cause problems in most patients within laboratory parameters at the dosages tested over 6 months. The proposed intake of 2. or 5. drug lymphocyte product.21. 22. and one patient developed a liver dysfunction-related food allergy. The European Food Safety Authority (EFSA) has recently carried out a safety assessment for Lentinex. 3. Lentinex consists of approximately 98 % water and 2 % dry matter (beta-glucan lentinan. Adverse events were observed in 9 patients (12%). The symptoms for this condition usually improve rapidly. in cancer patients in remission has recently been completed.7 mug/kg body weight for a 60 kg person.6. or after corticosteroid administration via a nasal spray.. supporting previous studies that the ABM product is generally safe.1 Summary of Hypersensitivity Studies Spores of mushrooms are airborne components and can be the cause of hypersensitivity / respiratory allergy. as a novel food ingredient in the context of Regulation (EC) No 258/97. Food Safety Studies A Phase I Clinical Trial of the dietary supplement. 2011). either without medication. and hence this condition has been referred to as ‘mushroom worker’s disease’. with most being digestive in nature such as nausea and diarrhoea. where air-quality may be poor. an aqueous mycelial extract of Lentinula edodes (Shiitake mushroom).5 mL Lentinex containing 1 mg lentinan (beta-glucan)/mL corresponds to 41. Agaricus blazei Murill (ABM). excluding possible allergic reaction (Ohno et al.

cross-over intervention study has investigated the effects of 4 weeks Lingzhi (Ganoderma lucidum) supplementation on a range of biomarkers for antioxidant status. and antioxidant capacity in urine increased.consumption of the mushroom Lentinula edodes and of other beta-glucan sources. and that 10 day supplementation was associated with a trend towards an improved CHD biomarker profile. immune status. aged 22-52 years) was collected before and after 4 weeks supplementation with a commercially available encapsulated Lingzhi preparation (1. An issue regarding significant amounts of nicotine in dried wild mushrooms (mainly Boletus edulis from China) was reported to the European Commission which resulted in the European Food Safety Authority (EFSA) proposing temporary maximum residue levels of 0. The study was performed as a follow-up to a study that showed that antioxidant power in plasma increased after Lingzhi ingestion. 2004). EFSA noted the presence of soy peptides in the culture medium. EFSA concluded that such a risk was expected not to be higher than that resulting from the normal consumption of the fruiting body of Lentinula edodes. cardiovascular disease (CHD) risk. Ukawa and colleagues (Ukawa et al. adverse effects reported after the consumption of the fruiting body of the Shiitake mushroom were not considered relevant. Owing to the fermentative production of the novel food ingredient from the mycelium and the final application of a heat-induced sterilisation step in various food products.2g fresh mushroom/d) or placebo.3 mg/kg for dried ceps only). A double-blind.17 mg/kg for dried wild mushrooms (2.. placebo-controlled. equivalent to 13. consenting adults (n=18. renal or DNA toxicity with Lingzhi intake (Wachtel-Galor et al. DNA damage. The EFSA also highlighted the necessity for a monitoring and testing programme to be launched by food business operators at the start of the 2009 harvest season. 2010). An LC-MS/MS system has been described and validated that provides a quick and sensitive analytical method for routine analysis of nicotine in fresh and dried mushrooms (Cavalieri et al. as well as markers of liver and renal toxicity. The animal and human studies provided by the applicant to EFSA were primarily carried out to determine the efficacy of the novel food ingredient. Although an allergenic risk cannot be excluded for sensitive subjects. 2007) have described the oral administration of 144 . although a slight trend toward lower lipids was seen.44g Lingzhi/d. 2010). No significant change in any of the variables was found. Fasting blood and urine from healthy. they were supporting but of limited value regarding a safety assessment.036 mg/kg for fresh wild mushrooms and 1.. and inflammation. The safety of Lentinex as a novel food ingredient was established at the proposed conditions of use and the proposed levels of intake (EFSA Panel on Dietetic Products and Allergies.. The results showed no evidence of liver.

.. A series of toxicological studies were conducted on a freeze dried preparation of AHCC (AHCC-FD).M. blood pressure and body measurement checks. Similarly. during which the authors assessed blood tests. 3000. The “no observed-adverse-effect level “(NOAEL) was considered to be 3000mg/kg body weight/day (Fujii et al. Histopathological changes related to AHCC-FD administration were observed in the limiting ridge of the stomach and in the liver of the high-dose group. and no changes attributable to AHCCFD treatment were observed in overall condition.1 Animal Model Studies The toxicological safety of an extract from cultured Lentinula edodes mycelia (L. analysis of agaritine from hot-water extracts of Hatakeshimeji showed no clinical effects suggesting that the extract of Hatakeshimeji was a safe food product. Sprague-Dawley rats were administered 1000. glucose and lipid metabolisms.E. it was considered of no toxicological significance.M extract. but as this finding was associated with decreased urinary pH and no evidence of kidney dysfunction was observed. In a 90-day study. hematology and clinical chemistry parameters. or 6000mg/kg body weight/day by gavage. Changes in urinary pH values observed in high-dose animals and middose females were considered physiological rather than adverse effects given the acidic nature of AHCC-FD. No mortality or abnormality in the general status or appearance was observed in rats administered L. 2011).E. 2011).M..) has been determined using repeated doses (2. extract was considered to be more than 2. and absolute and relative organ weights. hepatic and renal functions. 2010). Urinary protein also was increased in the same dose groups. ophthalmology findings. is used in Japan as a dietary supplement to boost immune function. The no observed adverse effect level (NOAEL) of L. There were no clinical problems observed with regard to blood test results. The effects of AHCC from Lentinula edodes and its use as a complementary therapy in patients with cancer has recently been reviewed (Shah et al.000 mg/kg/day (Yoshioka et al. The study reported no clinically significant changes related to toxicity. urine tests.4 linked glucans.(Hatakeshimeji) to adults (n=11) for two weeks.000 mg/kg/day) to male and female Wistar rats for 28 days. AHCC-FD was not mutagenic to Salmonella Typhimurium and did not exhibit clastogenicity in a mouse micronucleus assay.E.Lyophyllum decastes Sing. food consumption. a mushroom extract rich in alpha-1. 145 . and blood pressure. Active Hexose Correlated Compound (AHCC). 22. body weight.

6)-glucan in mushrooms.. glutamic acid and cysteine. A control group was given a basal diet without A. 1991). urinalysis or terminal necropsy (gross or histopathology findings) were noted. Based on the subchronic study. a polymer of beta-(1. Acute toxicity studies of a lectin from a saline extract of the fruiting bodies of the Shiitake mushroom. The lectin had no covalently-linked carbohydrate and amino acid composition analysis revealed that it contained 124 amino acid residues and was rich in tyrosine. Mortality in male treatment (mushroom) groups was significantly lower than in controls. the highest dose tested in the study (Chen et al. Female Charles River Sprague . Sub-chronic toxicity and mutagenicity studies were conducted Sprague Dawley rats. 2008). Histopathological studies showed no increased incidence of tumours. The results of mutagenicity studies as evaluated by gene mutations in Salmonella Typhimurium. has been assess for safety for use as a dietary supplement and food ingredient. A study to evaluate the chronic toxicity and oncogenicity of Agaricus blazei Murill in F344 rats has been reported (Lee et al. bisporus for 500 days. and organ weights compared to the control group. bisporus was observed in this long-term study (Matsumoto et al. arginine. Lentinula edodes (Berk). serum chemistry parameters. body weight gains. body weight gain.Dawley rats were fed a diet containing a 30% dry powder of A.3/1.. ophthalmic examinations. There was no significant difference in the incidence of tumours between the experimental group and control group. 1000 and 2000 mg/kg body weight (bw)/day for 90 days. Long-term (2 years) feeding of rats of a powdered diet containing Agaricus blazei at levels up to 25. LEL did not cause mortality. 12 rats/sex/group) were administered (gavage) mushroom beta-glucan at dose levels of 0. No carcinogenic activity of A. Long term Agaricus bisporus consumption has been studied in rats. Administration of beta-glucan did not result in any toxicologically significant treatment-related changes in clinical observations. in vitro chromosome aberrations and in vivo micronucleus test in mouse did not reveal any genotoxicity of beta-glucan.Beta-glucan. No adverse effects of the beta-glucan on the hematology. body weights. feed consumption. In the sub-chronic toxicity study. proline. bisporus. hematologic or serum chemistry parameters.000 ppm (parts per million) revealed no remarkable change in mean body weight. or absolute or relative organ weights in control or treatment groups. the no observed-adverse-effect level (NOAEL) for mushroom beta-glucan was determined to be 2000 mg/kg bw/day.. 2011c). phenylalanine. 500. nor was it observed to alter the morphology of key organs when administered 146 .

All animals survived to the end of the study. 2200 and 1500 mg/kg BW/day were given for 90 consecutive days and reverse osmosis water was used as control.. There was no mortality or signs of toxicity in the acute and subchronic toxicity studies under the above conditions (Hor et al. no abnormal changes were observed in clinical signs. hematology and serum biochemistry parameters between the treatment and control groups. Necropsy and histopathological examination indicated no treatment-related changes... 2011b). 2011). During the experiment period.. 147 . 2011a). 2011). 22.. The potential toxicity of Coriolus versicolor standardized water extract after acute and subchronic administration in rats has been studied. the extract was administered orally at doses of 1250. A further toxicological study on this mushroom in pregnant Sprague Dawley rats concluded that this mushroom has no teratogenic effects in female rats (Chen Tai et al. 2500 and 5000 mg/kg/day for 28 days to male and female SD rats respectively. 2010a). In the subchronic toxicity study. No significant differences were found in urinalysis. 2500 and 5000 mg/kg.000 mg/kg body weight of mice (Eghianruwa et al. Coriolus versicolor water extract was administered by oral gavage to Sprague-Dawley (SD) rats (6 males. 2011). 6 females) at single doses of 1250. body weight and ophthalmological examinations. Doses of 3000. A 90-day sub-chronic oral toxicological assessment of Antrodia cinnamomea.2 Agaritine Agaritine purified from Agaricus blazei Murrill has previously been shown to inhibit the proliferation of a number of human leukemic cell lines (Endo et al. In the acute toxicity study. The no-observed-adverse-effect level (NOAEL) of Antrodia cinnamomea was identified to be greater than 3000 mg/kg BW/day (the highest dose tested in this study) in Sprague-Dawley rats (Chen Tai et al. a medicinal mushroom has also been recently completed in 80 Sprague-Dawley rats..intraperitoneally at concentrations up to 10. A more recent study by the same group has now shown that the mechanism by which agaritine acts in U937 leukemic cells is via the moderate induction of apoptosis via caspase activation through cytochrome C release from mitochondria (Akiyama et al.

which further strengthens this evidence. which are recognised by pattern-recognition receptors on immune cells such as monocytes. balance of T helper cell (TH1 and TH2 in particular) populations and subsequent effects on natural killer (NK). 2010b). 2004). 23. Polysaccharides from mushrooms. Mushroom bioactive compounds and proposed mechanisms Recent studies on mushrooms and their extracts (Tables 7 and 8). Some of the more efficacious compounds in mushrooms are 1. the scientific validity of the experimental designs and models from which this conclusion has been drawn have been contradicted and challenged by other studies. have identified roles involving host-mediated immunomodulatory responses. While the majority of these mechanisms have been determined in in vitro or in vivo animal studies. 2010).. some recent data have also provided evidence for such immunomodulatory effects (increased NK cell activity. neutrophil and leukocyte counts) in humans from oral ingestion of dietary polysaccharides (glucans) from some varieties of mushrooms (Ramberg et al. via stimulation of both innate and adaptive immune pathways. A review of the available evidence has concluded that agaritine from consumption of cultivated Agaricus bisporus mushrooms poses no known toxicological risk to healthy humans (Roupas et al. generally belonging to the β-glucan family appear to inhibit tumor growth by stimulating the immune system. polysaccharides with other sugar moieties such as α-glucans have also been implicated (Borchers et al. 2008) while other studies with non-medicinal mushrooms containing 1.Although agaritine has been described in some studies as a potential carcinogen.3-β-glucans. IgM. with implications for inhibition of tumor growth via anti-proliferative effects and induction of apoptosis in human cancer cells. effects on IgG..6-branched 1. Apoptosis and/or anti-proliferative effects on carcinomas and cell lines is a mechanism shared by several mushrooms and their extracts in studies of anti-cancer effects. Beta-glucans in mushrooms are also known to exert immunomodulatory effects via activation of macrophages. cells and also via cytokine production (Hetland et al.4-glucans have not shown similar effects suggesting that branching of the βglucans may provide specificity to the binding of these compounds to immune cells. In addition to β-glucans. granulocytes and dendritic cells. The anti-tumor effects of proteoglycan fractions of mushrooms involve the elevation of natural killer (NK) cell 148 .

bioactive proteins from mushrooms (such as lectins. although such direct links have not been established to date. present in mushrooms of the Agaricus family.. 2006) and subsequent reduction of estrogen. In addition to the apoptotic and anti-proliferative effects. ergosterol and agaritine.. while the majority of such mechanisms have been determined in in vitro or in vivo animal studies. While the effects and underlying mechanisms of mushroom polysaccharides in health outcomes have been more extensively evaluated. NF-kappaB. 2010b).. anti-viral and immunomodulatory activities. fungal immunomodulatory proteins (FIP). 149 .numbers and the stimulation of inducible NO synthase gene expression. ribosome inactivating proteins (RIP). mushroom polysaccharides in particular are beginning to be evaluated as adjuvant cancer therapy compounds alongside conventional cancer treatments (Standish et al. particularly in breast cancer patients with estrogen receptor positive tumors where mushroom extracts have been shown to inhibit aromatase activity (Grube et al. ribonucleases and other proteins have also been reported to possess anti-tumor. the anti-inflammatory and anti-microbial / viral effects outlined may also contribute to the anti-carcinogenic effects of mushrooms and their extracts. 2001. which is then followed by NO production in macrophages via activation of the transcription factor. Activation of NK cells is likely via interferon-gamma and interleukin mediated pathways. Furthermore. As mentioned above. Chen et al. have been reported to inhibit proliferation of leukemic cells without effects on normal lymphatic cells and that this activity was distinct from that of β-glucan (Endo et al. 2008)..

randomized. Mushroom Varieties – Effects on Health Agaricus bisporus (common white button. Furthermore. A randomised trial of 24 healthy volunteers has shown that consumption of 100 g of blanched Agaricus bisporus daily with a normal diet for 1 wk significantly accelerated sIgA secretion. portabella) Secretory immunoglobulin A (sIgA) acts as the first line of adaptive humoral immune defense at mucosal surfaces.24.. diets containing 2. Vitamin D2 from UVB-exposed mushrooms was reported to be bioavailable. and functional in supporting bone growth and mineralization in a 150 . because 25-hydroxycholecalciferol (25(OH)D3) decreased proportionally in serum (Stephensen et al. Exposing white button mushrooms to ultraviolet B (UVB) light markedly increases their vitamin D2 content. placebo-controlled trial (registered at http://germanctr. In weanling female rats.de as DRKS00000195) in 26 young subjects with serum 25-hydroxyvitamin D (25OHD) < 50 nmol/l undertaken over a 5 week period has demonstrated the bioavailability of vitamin D2 from UV-B-irradiated button mushrooms in healthy adults deficient in serum 25-hydroxyvitamin D.0% mushroom unexposed to light. the bioavailability of vitamin D2 from vitamin D2-enhanced button mushrooms via UV-B irradiation was effective in improving vitamin D status and not different to a vitamin D2 supplement (Urbain et al. 2011). safe... A recent randomised controlled trial of 38 adults consuming ergocalciferol from Agaricus bisporus or supplements for 6 weeks has reported that ergocalciferol was absorbed and metabolized to 25-hydroxyergocalciferol (25(OH)D2) but did not affect vitamin D status. brown / crimini. thereby indicating its effect on the improvement of mucosal immunity (Jeong et al.0% light-exposed mushrooms significantly raised 25-hydroxyvitamin D (25(OH)D) and suppressed parathyroid hormone levels compared to control-fed rats or rats fed 5.5% and 5. 2012). 2011). A single-blinded.

while exposure to sunlight resulted in a 26% loss of riboflavin. no significant changes in vitamin C. niacin. 2010b). which are associated with cardiovascular disease (Martin. Lentinula edodes (shiitake). and unexplained increases in ergosterol (9. the mushroom species with the highest antioxidant potential was Agaricus bispous (brown). ergosterol.5%) (Simon et al. L. Vitamin D2 can be increased by UV-B exposure during the growth phase of Agaricus bisporus. which can lead to discoloration. 151 .. in vivo samples revealed higher antioxidant properties than their mycelia obtained by in vitro techniques. fatty acids. 2012). edodes possessed the highest reducing power. 2010a). A comparison has been undertaken of the antioxidant properties and phenolic profile of the most commonly consumed fresh cultivated mushrooms and their mycelia produced in vitro: Agaricus bisporus (white and brown). Generally. A further study by the same group reported that ergothioneine. folate. Of the mushrooms evaluated. exposure of whole or sliced mushrooms to pulsed UV light significantly increased vitamin D2 without any observed discoloration (Rao Koyyalamudi et al. Pleurotus ostreatus (oyster).. and to inhibit monocyte binding to endothelial cells characteristic of early cardiovascular disease (Martin. was able to interrupt proinflammatory induction of adhesion molecule expression associated with atherogenesis.growing rat model without evidence of toxicity (Calvo et al. riboflavin. and Grifola frondosa (maitake) mushrooms have been shown to inhibit adhesion molecule expression and in vitro binding of monocytes to human aortic endothelial cells under pro-inflammatory conditions. 2011). Growth is unaffected by UV-B.. however.. 2012). Pleurotus ostreatus (oyster). vitamins B 6.. vitamin B 5. On a dry weight basis. evidence of folate oxidation. Post-harvest exposure to supplementary UV-B resulted in a higher vitamin D2 content of 32 mg/100 g compared to 24 µg/100 g obtained from exposure to UV-B during the growth phase (Kristensen et al. The effects of UVB on Agaricus bisporus are limited to changes in vitamin D and show no detrimental changes relative to natural sunlight exposure. or agaritine were observed following UVB processing. Pleurotus eryngii (king oyster) and Lentinula edodes (shiitake). amino acids. Agaricus bisporus (white button and crimini). with in vitro. 2011). There was no correlation between the studied commercial mushrooms and the corresponding mycelia obtained in vitro (Reis et al. Enrichment of vitamin D 2 in Agaricus bisporus white button mushroom using continuous UV light needs a longer exposure time. 2012). an antioxidant present in edible mushrooms.

n-nonane.05-76. Mg. K. (Caglarirmak.2-554. Agaricus Bisporus has been shown to significantly lower liver weight and hepatic injury markers in ovariectomized mice (a model of postmenopausal women).40-7. 88.96.29-238. as well as anticandidal activity against Candida albicans by the Agaricus bisporus extracts as well as inhibition of cell proliferation of HL-60 leukemia via the induction of apoptosis. Ergothioneine was bioavailable after consuming mushrooms (8g and 16g) and a trend in the postprandial triglyceride response indicated that there was a blunting effect after both the 8g and 16g ergothioneine doses were compared with the control (0g dose).09. 1180. riboflavin.08. Dietary intake of white button mushroom. the mean contents were 6. 0.97.82. Genes related to the fatty acid biosynthesis pathway.or 16-carbon compounds such as octadecanoic acid. 0.The bioavailability of ergothioneine from Agaricus bisporus. benzendicarboxylic acid. 2012). In vitro mechanistic studies using the HepG2 cell line showed that down-regulation of the expression of FAS and ELOVL6 by this mushroom extract was through inhibition of 152 . hexadecanoic acid derivatives. 213. and consumption was associated with an attenuated postprandial triglyceride response (Weigand-Heller et al. and 3. and cis-linoleic acid esters.0-2500. cross-over. Analyses of Agaricus bisporus (brown). were down-regulated in the liver of mushroom-fed mice. and Ca contents of both harvests were 8. and other important volatiles like di-limonene. The estimated volatile components comprised 18. This study also reported antibacterial activity against both gram positive and gram negative bacteria.157.75-3. and 534. and the mice had improved glucose clearance ability. Ergothioneine from A..085-0.29. Fe.94 mg/kg.07. There was less fat accumulation in the livers of mice on the mushroom diet. postprandial time-course design.7. 0. dose-response.27-0. that functions as an antioxidant in mushrooms has been determined in a pilot study in healthy men (n=10) using a randomized. respectively. It is of interest to note that the antioxidant (free radical-scavenging) activity reported in ethanol extracts of Agaricus bisporus as well as the total phenolic and flavonoid concentration are similar before and after boiling (Jagadish et al. in three flushes and at two different harvest times showed the mean Zn. 2009).93-1038. thiamin. 2652.29. In terms of vitamin C. 2009).09-0. particularly the genes for fatty acid synthetase (Fas) and fatty acid elongase 6 ( Elovl6).80 mg/kg. P. and niacin.89. folic acid..69. bisporus mushrooms was therefore bioavailable as assessed by red blood cell uptake postprandially. Na.622. respectively.

Two polysaccharide fractions (designated as ABP-1 and ABP-2) isolated from Agaricus bisporus have been shown to stimulate the production of nitric oxide. 2011b). As only conjugated linoleic acid was found to inhibit the testosterone-dependent proliferation of MCF-7aro cells. Whereas these results suggest that these two compounds bind to the active site of aromatase. as they suppress aromatase activity and estrogen biosynthesis. the inhibition kinetic analysis indicated that they are non-competitive inhibitors with respect to androstenedione. Coprinus comatus. 2006). A recent study has evaluated the activity of mushroom extracts in the estrogen receptor-positive/aromatase-positive MCF-7aro cell line in vitro and in vivo. 2012. Most potent mushroom chemicals are soluble in ethyl acetate. The in vivo action of mushroom chemicals was shown using nude mice injected with MCF-7aro cells. or spores of Ganoderma lucidum) stimulated nitric oxide production by 153 . The major active compounds found in the ethyl acetate fraction were unsaturated fatty acids such as linoleic acid. Both ABP-1 and ABP-2 had the ability to inhibit the growth of human breast cancer MCF-7 cells but had little effect on the growth of human colon. These data provide evidence that macrophages possibly contribute to the antitumorigenic effects of Agaricus bisporus polysaccharides (Jeong et al. Mushroom extract decreased testosterone-induced cell proliferation in MCF-7aro cells but had no effect on MCF-10A. Beta-glucan-rich polysaccharide extracts from Agaricus bisporus (but not A. a non-tumourigenic cell line. The studies showed that the mushroom extract decreased both tumour cell proliferation and tumour weight with no effect on the rate of apoptosis (Chen et al.. Modulation of macrophage function by A. The interaction of linoleic acid and conjugated linoleic acid with aromatase mutants expressed in Chinese hamster ovary cells showed that these fatty acids inhibited aromatase with similar potency and that mutations at the active site regions affect its interaction with these two fatty acids. and tumor necrosis factor-alpha..liver X receptor (LXR) signalling and its downstream transcriptional factor SREBP1c (Kanaya et al.. blazei Murill. gastric cancer. when murine Sarcoma 180 cells exposed to ABP-1 or ABP2 were implanted subcutaneously into mice. Phellinus linteus. bisporus polysaccharides was mediated in part through activation of nuclear factor-kappaB.. However. interleukin-6. linolenic acid. the physiologically relevant aromatase inhibitors in mushrooms are most likely conjugated linoleic acid and its derivatives. and conjugated linoleic acid. and murine Sarcoma 180 cells. 2012). Extracts from Agaricus bisporous mushrooms have been suggested as potential breast cancer chemopreventive agents. Sang Chul et al. prostate. a reduction in tumor growth was observed compared with that observed in control mice.

154 . It has been demonstrated that dietary supplementation with white button mushrooms (Agaricus bisporus) enhances natural killer (NK) cell activity in C57BL/6 mice. IL-1beta and IL6 mRNAs expression in response to LPS stimulation (Moro et al..3-GalNAc-binding lectin. MCF-7 breast cancer cells by 50%. 2002). It has been suggested that branching of the betaglucan chain is essential for immune-stimulating activity (Volman et al.. a double-blind randomized trial has been undertaken in 56 mildly hypercholesterolemic subjects who consumed a control fruit juice with or without added alpha-glucans with the authors suggesting that in vivo. cibarius and L.bone marrow-derived macrophages. from the edible mushroom Agaricus bisporus lectin (ABL) has been evaluated. similar inhibition of proliferation of HT29 cells by ABL was found. 2007a). alpha-glucans had lost their efficacy to stimulate the immune response as observed in an in vitro mouse model (Volman et al. Cantherellus cibarius. 2012). 2010a).. ABL (25mg/ml) inhibited incorporation of [3H]-thymidine into DNA of HT29 colon cancer cells by 87%. Boletus edulis. Human ocular fibroblasts in monolayers and in three-dimensional collagen lattices were exposed to Agaricus bisporus (0-100 µg/ml). Agaricus bisporus caused a dose-dependent inhibition of proliferation and lattice contraction without significant toxicity.7macrophages. Lactarius deliciosus and Pleurotus ostreatus have shown antiinflammatory activity in LPS activated RAW 264. although further studies are required (Batterbury et al. A study has been undertaken to determine whether it might have inhibitory activity on Tenon's capsule fibroblasts in in vitro models of wound healing and therefore have a use in the modification of scar formation after glaucoma surgery. However. Caco-2 colon cancer cells by 16%. A. The effect on epithelial cells of a Gal beta-1. C.. bisporus. When assessed by cell count.deliciosus exhibited the higher anti-inflammatory activities inducing inhibition of NO production and iNOS. Methanol extracts from Agaricus bisporus. and Rama-27 rat mammary fibroblasts by 55% when these cells were grown for 24h in serum-free medium. 2010b). suggesting that increased intake of white button mushrooms may promote innate immunity against tumours and viruses through the enhancement of NK activity (Wu et al. The edible mushroom lectin from Agaricus bisporus has been reported to have antiproliferative effects on a range of cell types. Cratarelluscornucopioides. The data showed that Agaricus bisporus possesses key features required of an agent that might control scarring processes and suggest that Agaricus bisporus may be especially useful where subtle modification of healing may be needed..

2002). 2005). The STZ-induced diabetic male Sprague-Dawley rats fed Agaricus bisporus powder (200 mg/kg of body weight) for 3 weeks had significantly reduced plasma glucose 155 . 2000). MCF-7. mediator of the anti-proliferative effects of the protein.. and Rama-27 cells as measured by trypan blue exclusion.2mg/ml) caused no cytotoxicity to HT29. A heat-labile protein has also been identified in fruit bodies of Agaricus bisporus which protects Raji cells (a human lymphoma cell line) against H2O2-induced oxidative damage to cellular DNA (Shi et al. with little degradation of the lectin.. A. and inhibition of proliferation in HT29 cells caused by 50mg/ml ABL was reversible after removal of the lectin. Aqueous extracts of the sporophores of eight mushroom species have been assessed for their ability to prevent H2O2-induced oxidative damage to cellular DNA using the singlecell gel electrophoresis ("Comet") assay.ABL (0. 2010). binds at a shallow depression on the surface of the molecule. reflects the tendency of lectins to resist biodegradation and implies that other endogenous or exogenous lectins may be processed in this way by intestinal epithelial cells (Yu et al. Gal beta 1-3GalNAc. These edible mushrooms therefore represent a valuable source of biologically active compounds with potential for protecting cellular DNA from oxidative damage (Rocha et al. The highest genoprotective effects were obtained with cold (20ºC) and hot (100ºC) water extracts of Agaricus bisporus and Ganoderma lucidum fruit bodies. The lectin has two distinct binding sites per monomer that recognize the different configuration of a single epimeric hydroxyl (Carrizo et al. respectively. 1993). Agaricus bisporus has been shown to lower blood glucose and cholesterol levels in streptozotocin (STZ)-induced diabetic and rats fed a hypercholesterolemic diet (Jeong et al. The three-dimensional structure of the lectin from Agaricus bisporus has been determined by x-ray diffraction. 2002). and each monomer presents a novel fold with two beta sheets connected by a helix-loop-helix motif. The internalization and subsequent slow release... The reversibility of the anti-proliferative effect of Agaricus bisporus lectin is associated with its release from cancer cells after internalization.. The protein is a tetramer with 222 symmetry.. The Tantigen disaccharide. Extracts from Agaricus bisporus have also been shown to induce proapoptotic effects in the human leukemia cell line K562 (Shnyreva et al. bisporus lectin appears to be a reversible non-cytotoxic inhibitor of epithelial cell proliferation which deserves further study as a potential anti-cancer agent (Yu et al.. 2010).

oral feeding of the Agaricus bisporus powder for 4 weeks resulted in a significant decrease in plasma total cholesterol and low-density lipoprotein (22.. None of nine other lectins tested stimulated insulin release. low-density lipoprotein. a hot water extract of Agaricus bisporus. 2010). Maximal stimulation of insulin release was reported at lectin concentrations above 58mg/mL (approximately 1µM). nor did it modify rates of insulin secretion induced by 20 mM glucose. The data also suggesting that lectin binding is essential for the expression of insulin-releasing activity. Pseudomonas aeruginosa and Klebsiella pneumoniae were most sensitive to aqueous.and B-cells that facilitate exocytosis (Ewart et al. The lectin did not alter islet glucose oxidation to CO2 or incorporation of [3H] leucine into trichloracetic acid-precipitable material. liver enzyme activities. A hypoglycemic effect on streptozotocin-induced diabetic rats has been demonstrated by Agaricus bisporus (Sang Chul et al.. Agaricus bisporus and Pleurotus sajor caju have been assayed in vitro for their antimicrobial activities using aqueous and organic solvents extracts. 156 . The decreases in total cholesterol.and triglyceride concentrations (24. A similar significant decrease in hepatic cholesterol and triglyceride concentrations was observed (36. respectively). Furthermore. and liver weight gain. methanol and xylene extracts of these mushrooms (Tambekar et al. administered at 400 mg/kg body weight per day for 7 days resulted in a 29.1%. respectively). whereas stimulation of fat cell glucose oxidation was a general property of the lectins.68% reduction of serum glucose levels. with serum insulin levels significantly increasing in streptozotocin-induced diabetic rats. Enterobacter aerogenes. alanine aminotransferase and aspartate aminotransferase (11.7% and 39.2% and 20.8%. and triglyceride concentrations were accompanied by a significant increase in plasma high-density lipoprotein concentrations demonstrating significant hypoglycemic and hypolipidemic activity in rats. 2010). a most interesting effect of the treatment was the increase in cellularity of the Langerhans islets of the pancreas and their apparent repopulation with beta cells (Yamac et al. ethanol. In hypercholesterolemic rats.1%. Lectins from Agaricus bisporus and Agaricus campestris have been shown to stimulate insulin and glucagon release from isolated rat islets in the presence of 2 mM glucose.7% and 15.. It has been shown that Escherichia coli 390. 1975). respectively). However. 2006).. The authors proposed that the specific interaction between mushroom lectin and its receptors may lead to conformational changes in the structure of the membranes of the islet A2. respectively).8% and 33.7%. Escherichia coli 739.

baked at 220-230ºC for 10 minutes and subsequently fed to mice for 12h each day. 5-dihydroergosterol. 2001). has shown the isolation of two heterocyclic carboxylic acids. The estimated average daily mushroom consumption per animal was 4. No carcinogenic activity of A.8g for female mice and 4. and cerevisterol. and colon when compared to the untreated controls. namely Agaricus bisporus and Calocybe indica. Significant levels of pyridine-3-carboxylic acid (nicotinic acid) were found in C. 2000). volvacea and two other edible mushrooms. bisporus was observed in this long-term study (Matsumoto et al. namely pyridine-3-carboxylic acid [nicotinic acid] and pyrazole-3(5)-carboxylic acid and four steroidal metabolites ergosterol. 157 . bisporus for 500 days. Shiitake (Lentinus edodes) fiber.. showed no statistically significant difference in tumours in the lungs. blood vessels. 1991).2g for male mice (Toth et al. The results demonstrated that mushroom fiber (and sugar beet fiber) lowered the serum total cholesterol level by enhancement of the hepatic low density lipoprotein (LDL) receptor mRNA (Fukushima et al. There was no significant difference in the incidence of tumours between the experimental group and control group. bisporus. A control group was given a basal diet without A. Correlations have been suggested between the occurrence of these compounds in mushrooms and consumption as well as beneficial health effects (Mallavadhani et al. five days each week throughout their life and also fed a well-balanced semi-synthetic diet for 12h each day for five days and for the remaining two full days each week. 2006). the levels of pyridine-3-carboxylic acid and pyrazole3(5)-carboxylic acid were estimated in V.A report on the fractionation of extracts of the edible mushroom. ergosterol peroxide. which exceeds the average daily consumption of mushrooms by humans (Shephard et al. and pyrazole-3(5)-carboxylic acid was found in abundance in A.. Plasma cholesterol concentration in rats has been shown to be reduced by feeding of mushroom (Agaricus bisporus) fiber.. cecum. In light of the structural similarity of pyrazole-3(5)-carboxylic acid to pyrazole-3-carboxylic acids. 1995).. indica. Volvariella volvacea. 1997)... Similar cholesterollowering effects in rats of Maitake (Grifola frondosa) fiber. Long term Agaricus bisporus consumption has been studied in rats. and Enokitake (Flammulina velutipes) fiber have also been reported (Fukushima et al.Dawley rats were fed a diet containing a 30% dry powder of A. bisporus. which act as agonists for nicotinic acid receptors. Female Charles River Sprague . A study by Toth and co-workers in which Agaricus bisporus.

in cancer patients in remission has recently been completed. Phaseolus vulgaris. only 23% of WBM and 29% of SM mice did (P = 0. 3. The effects of white button mushrooms (WBM) and shiitake mushrooms (SM) on collageninduced arthritis (CIA) have been studied in 8-wk-old female dilute brown non-agouti mice. excluding possible allergic reaction (Ohno et al.8.0.1).95 (P = 0.4 g ABM granulated powder per day orally for 6 months. Whereas 58% of control mice had a CIA index 7. and further studies are needed to confirm such effects. Compared to the control diet.. 158 . While these data provide some suggested benefits in this animal model. none of the adverse events occurred in a dose-dependent manner. 2011). with most being digestive in nature such as nausea and diarrhoea. statistical validation of these data is borderline. The study showed that ABM does not cause problems in most patients within laboratory parameters at the dosages tested over 6 months. 2001).15 +/. WBM and SM tended to reduce the CIA index from 5. Ricinus communis and its constituent chains have been shown to inhibit human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (Wang and Ng.. 2008). respectively).82 to 3. supporting previous studies that the ABM product is generally safe. Momordica charantia. SM). Although both types of mushrooms reduced plasma TNF alpha (34%. Cancer survivors took 1.05) (Chandra et al. WBM.3-fold (P < 0. and one patient developed a liver dysfunction-related food allergy. Adverse events were observed in 9 patients (12%). Seventy-eight patients were assessed for safety of ABM (30/24/24 subjects at 1/2/3 packs per day.Lectins from Agaricus bisporus. bisporus strongly generated reactive oxygen species (suggesting immunomodulatory effects) in human PBMCs and K 562 cells in vitro (Wei et al.11 +/0. Agaricus blazei Murill (ABM). Agaricus blazei A Phase I Clinical Trial of the dietary supplement.06) (median.. 64%. 2011a). drug lymphocyte product.6. or 5. only SM increased plasma IL-6 by 1. 6-9 to 1-2) 31 d post-collagen injection. However. while phenolic compounds present in extracts from A.

but the AbM-based extract resulted in increased production of proinflammatory. 159 . A randomized. The increase in adiponectin concentration after taking Agaricus blazei Murill extract for 12 weeks may be the mechanism that results in the observed effect (Hsu et al. placebo-controlled trial has evaluated the effects of Agaricus blazei Murrill intake (900 mg/day for 60 days) on serum levels of interleukin-6 (IL-6). interferon-gamma (IFN-gamma) and tumour necrosis factor-alpha (TNF-alpha) in 57 community-living elderly women. and no significant anticancer effects were observed with the intake of these two mushroom supplements (Yoshimura et al. 2010). 2010) . containing extracts from the Agaricus blazei Murill mushroom. Ingestion of an AbM-based medicinal mushroom by patients with IBD resulted in decreased levels of pathogenic cytokines in blood and calprotectin in faeces. After 60 days. no changes from baseline were detectable for any parameter in either the placebo (n=29) or the mushroom (n=28) group (Lima et al. pointing to an antiinflammatory effect. Supplementation of Agaricus blazei Murill extract improved insulin resistance among subjects with type 2 diabetes.. although an in vitro study by the same authors with monocyte-derived dendritic cells showed that AbM did not induce increased synthesis of Th2 or anti-inflammatory cytokines or the Th1 cytokine IL-12.A randomized. The mechanisms for such effects are unclear. 2007). Faecal calprotectin (a marker for inflammatory bowel disease (IBD) was reduced in the UC group. double-blind... containing the Ganoderma lucidum mushroom has reported no serious adverse effects. A 6 month open-label study in 51 patients with prostate cancer that ingested either Senseiro.. and placebo-controlled clinical trial has evaluated the effects of Agaricus blazei Murill in combination with metformin and gliclazide on insulin resistance in type 2 diabetes. or Rokkaku Reishi. 2012). 2011). An extract (AndoSan) from Agaricus blazei Murill (AbM) has been shown to reduce blood cytokine levels in healthy volunteers after 12 days of ingestion.. n=10) and Crohn's disease (CD. suggesting anti-inflammatory effects (Forland et al. n=11) in which baseline concentrations for the (17) cytokines ebaluated in the UC and CD patient groups were largely similar. double-blinded. This extract also modulated cytokines in patients with ulcerative colitis (UC. chemotactic and some Th1-type cytokines (Forland et al.

TNF-alpha (84%). a hot water extract of Agaricus blazei Murrill (ABM) powder was fractionated by HPLC based on the anti-tumour activity against leukemic cells in vitro. having a molecular mass of 267Da. IL-17 (50%) and IL-2 (46%). mainly containing AbM. but showed no significant effect on normal lymphatic cells. in vivo in the eight volunteers who completed the daily intake (60 ml) of this AbM extract for 12 days. This compound inhibited the proliferation of leukemic cell lines such as U937. 2009). However. which indirectly suppresses proliferation of tumour cells. extracted from the mycelia of Agaricus blazei and Lentinus edodes. ABCL) on human volunteers with C-type hepatitis has been studied.5-5. The data also showed that this activity was distinct from that of beta-glucan.. HL60 and K562. Agaritine purified from Agaricus blazei Murrill has been shown to exert anti-tumour activity against leukemic cells (Endo et al. ranging from two to 399-fold (TNFalpha). The data demonstrated a weightcontrolling and hypolipidemic effect of both A-PBP and L-PBP via a mechanism involving absorption of cholesterol (Kweon et al. nor other side effects were observed (Inuzuka and Yoshida. 2002). a significant reduction was observed in levels of IL-1-beta (97%). there was a dose-dependent increase in all the cytokines studied.Clinical effects and safety evaluation of Agaricus Blazei Condensed Liquid (Agaricus Mushroom Extract. on serum cholesterol and body weight have been investigated in 90 female volunteers. A total of 20 patients (10 male. In this study. After stimulation of whole blood ex vivo with 0. 10 female) with chronic C-type hepatitis received the ABCL orally twice per day for 8 weeks.. 160 . No toxicological effects. 2002). The discrepant results on cytokine release ex vivo and in vivo may partly be explained by the antioxidant activity of AbM in vivo and limited absorption of its large beta-glucans across the intestinal mucosa to the reticuloendothelial system and blood. Another nine cytokines were measured but they were unaltered.. beta-N(gamma-l(+)-glutamyl)-4-(hydroxymethyl) phenylhydrazine. The authors concluded that agaritine has direct anti-tumour activity against leukemic tumor cells in vitro which is in contrast to the carcinogenic activity previously ascribed to this compound. The purified substance was identified as agaritine. MOLT4. The effect of Agaricus blazei Murill (AbM) on the release of several cytokines in human whole blood both after stimulation ex vivo and in vivo after oral intake over several days has been studied in healthy volunteers (Johnson et al. The effects of protein-bound polysaccharides (A-PBP and L-PBP).0% of a mushroom extract. 2010b).

NK cell cytotoxicty was augmented with the same extracts. interleukin-1 (IL-1) and IL-8. oral administration of Agaricus blazei water extracts to mice has been shown to induce the activation of macrophages and T cells in vivo. C3H/HeJ. the anti-tumour activity of Agaricus blazei appears to be mainly due to the activation of the immune system rather than to any direct effects on tumour cells. and BALB/c mice. Both parameters were largely inhibited by neutralizing anti-interleukin-12 (IL-12) monoclonal antibody (mAb) and completely inhibited when anti-IL-12 mAb and anti-IL-18 mAb were used in combination. under certain conditions. blazei failed to stimulate natural killer (NK) cell activity in murine spleen cells in vitro. in response to water extracts in in vitro experiments. Augmented cytotoxicity was demonstrated by purified NK cells from treated wildtype (WT) and RAG-2-deficient mice. anti-mutagenic and anti-clastogenic effects have also been detected in Agaricus blazei water extracts (Sorimachi and Koge. blazei by 161 . but not from interferon-gamma (IFN-gamma) deficient mice. but the strongest effect was observed in a 30% ethanolsoluble-50% ethanol-insoluble fraction prepared from the extract at 40ºC (fraction A-50). Aqueous extracts of Agaricus blazei fruiting body prepared at different temperatures have been fractionated by ethanol precipitation with various ethanol concentrations. Fraction A-50 also showed the strongest augmenting effect on interferon (IFN)-gamma production. This is supported by the fact that macrophages derived from rat bone marrow have been shown to be activated and cytokines such as tumour necrosis factor-alpha (TNF-α). NK cell activation and IFN-gamma production was also observed in vitro when dendritic cell (DC)-rich splenocytes of WT mice were coincubated with an extract of A. 2008). Polysaccharide fractions of Agaricus blazei have been prepared from cultured A. 2001). have also been shown to have anti-mutagenic activities in mice that may contribute to an anti-carcinogenic effect (Delmanto et al.In general. and nitric oxide (NO) were secreted. again in an IL-12 and IFN-gamma-dependent manner. Furthermore. These results demonstrate that A. blazei. An aqueous extract of the hemicellulase-digested compound of A. and this was completely inhibited by anti-IL-12 mAb alone. 2005). Oral administration of dried fruiting bodies of A. blazei has been shown to augment cytotoxicity of natural killer (NK) cells in wild-type (WT) C57BL/6. blazei and ABPC augmented NK cell activation through IL-12-mediated IFN-gamma production (Yuminamochi et al. blazei particle (ABPC) induced IFN-gamma production more effectively. The original aqueous extracts of A. This augmentation of NK activity and IFN-gamma production by fraction A-50 was completely abrogated by heat treatment (Zhong et al.. Agaricus blazei Murrill extracts. Antigenotoxic. 2007)...

3-beta-glucan segment forms the active centre of the anti-tumour activity (Ohno et al. 2007). The mice receiving A. iii) resistant to a 1. blazei extract exhibited significantly greater serum immunoglobulin G levels. In addition.3-beta-glucanase. the primary structures of AgHWE. Consumption of A. 2001).. anti-hypercholesterolemic. indicating that A. increased T-cell numbers in spleen. anti-hypertriglyceridemic. These fractions were found to be i) neutral beta-glucan passing DEAE-Sephadex A-25. enzymic. 2005b). the NaOH extracts showed anti-tumour activity against the solid form of Sarcoma 180 in ICR mice. ii) resistant to periodate oxidation (I/B) and subsequent partial acid hydrolysis (I/B/H). relating to general immune function or adaptive immunity against immunogen chicken ovalbumin. and anti-arteriosclerotic activity indicating overall anti-diabetic activity in diabetic rats. and then hot NaOH (AgHA).. and NMR analyses.3-beta glucosidic linkage was detectable in the 13 C-NMR spectrum. splenocyte proliferation rate. However. Agaricus blazei has also been reported to have inhibitory effects on mast cell-mediated anaphylaxis-like reactions (Choi et al.. although the number of in vivo studies is limited. after I/B/H treatment of the neutral fraction of AgCAE. before I/B. 2006b). By chemical. Nine parameters. Among these fractions. AgCA. A recent study has evaluated the immunomodulatory effects of A. To demonstrate the active component in these fractions. but sensitive after I/B/H. Beta-glucans and and their enzymatically hydrolyzed oligosaccharides from Agaricus blazei have anti-hyperglycemic. blazei extract or distilled water for 8 to 10 weeks. several chemical and enzymic treatments were applied. blazei Murill possesses a wide range of immunomodulatory effects in vivo (Chan et al. cold NaOH (AgCA).6-beta-glucan. The mice were divided into four groups and treated with various quantities of intragastric A. blazei in 160 male Balb/cByJ mice. Beta-glucans from Agaricus blazei have also been reported to not exert a genotoxic or 162 .. a signal around 86 ppm attributable to 1. and AgHA were mainly composed of 1.repeated extraction with hot water (AgHWE). delayed-type hypersensitivity. and tumour necrosis factoralpha secretion by splenocytes. Agaricus blazei Murill has been reported to possess biological effects that include immunomodulatory activities. These data strongly suggest that a highly branched 1. the enzymatically hydrolyzed oligosaccharides have been shown to have around twice the activity of beta-glucans with respect to anti-diabetogenic activity (Kim et al. were determined. zymolyase. blazei was also associated with significant increases in ovalbumin-specific serum immunoglobulin G level. and elevated phagocytic capability compared with controls.

. 2006). as to a particular increase in mRNA for the cytokines IL1A. as well as PTGS2 (cyclooxygenase2) (Ellertsen et al. has been reported to possess antimutagenic and anti-tumour effects. A study has investigated the effects of ABMK consumption on immunological status and quality of life in cancer patients undergoing chemotherapy. but that it does protect against DNA damage caused by benzo[a]pyrene in the human hepatoma cell line HepG2. whereas the activities of caspase 3 and the DNA fragmentation were enhanced the 163 . ovarian. blazei induced lactate dehydrogenase leakage in three cancer cell lines. AbM produced a unique profile. Both AbM and LPS had very significant effects on gene expression. with the authors suggesting that ABMK treatment may have some beneficial effects for gynecological cancer patients undergoing chemotherapy (Ahn et al. A. 2004). Genes related to immune function were selectively up-regulated. An extract from Agaricus blazei Murill Kyowa (ABMK).. and endometrial cancer patients were treated either with carboplatin (300mg/m2) plus VP16 (etoposide. particularly in a broth fraction. no significant difference in lymphokine-activated killer and monocyte activities was observed in a manner similar to the count of specific immune cell populations between ABMK-treated and non-treated groups. The data suggest that beta-glucan acts through binding to benzo[a]pyrene or the capture of free radicals produced during its activation (Angeli et al. CXCL2 and CXCL3. However.. blazei.g. inhibited cell proliferation in both androgen-dependent and androgen-independent prostate cancer cell lines. particularly pro-inflammatory genes such as the interleukins IL1B and IL8. The authors observed that natural killer cell activity was significantly higher in the ABMK-treated group compared to the non-treated placebo group (n = 61). CXCL1. e. Extracts from Agaricus blazei Murill (AbM) have been evaluated on changes to gene expression on a human monocyte cell line (THP-1). 100mg/m2) or with carboplatin (300mg/m2) plus taxol (175mg/m2) every 3 weeks for at least three cycles. Changes in the levels of mRNA transcripts were measured using 35 k microarrays. The effects of Agaricus blazei Murill on the growth of human prostate cancer have been examined in vitro and in vivo. alopecia. chemotherapyassociated side effects such as appetite. However. 2009).. and the changes in select cytokine gene products by immunoassays.mutagenic effect. Although most genes induced by AbM were also induced by LPS. with or without oral consumption of ABMK. One hundred cervical. emotional stability. Lipopolysaccharide (LPS) was included for comparison. The broth of A. and general weakness were all reported to be improved by ABMK treatment.

(containing the Ganoderma lucidum mushroom) have been evaluated over 6 months in patients with prostate cancer in Japan (Yoshimura et al. 2004). Ergosterol had no cytotoxicity against tumour cells and it appears as though the antitumour activity of ergosterol might be due to direct inhibition of angiogenesis induced by solid tumours (Takaku et al. No partial response in terms of serum prostate-specific antigen was observed.most in androgen-independent PC3 cells. as well as immune-modulatory activity. 2010). thymus. not only in the right flank. Administration of ergosterol for 20 days was reported to be without side effects.4-glucan-beta-1.. Serum 164 . Alteration of serum prostate-specific antigen doubling time did not correlate with that of serum testosterone levels. Oral supplementation with the broth of A. Ergosterol reduced tumour growth at doses of 400 and 800mg/kg. 2001). epididymal adipose tissue. Inoculation of a low molecule fraction (LM) into the primary tumour of a two-tumour mouse model resulted in a marked inhibition of the tumour. Oral administration of ergosterol. containing alpha1. The effects of low molecular weight products extracted from Agaricus blazei Murill on MethA tumour cell growth have been studied. 2009a).. Chromatographic purification and physicochemical characterization showed the main tumouricidal activity to be located in a low molecule fraction-3 (LM-3). Serious adverse effects were not observed and no significant anticancer effects were observed with the intake of these two mushrooms in the study population. such as decreases in body. Patients with biochemical failure after radical treatment for non-metastasized prostate cancer were enrolled in this open-label study. and spleen weights and leukocyte numbers induced by cancer chemotherapy drugs. in tumourbearing mice (Kimura et al. blazei (with the higher ratio of beta-glucan) significantly suppressed tumour growth without inducing adverse effects in severe combined immunodeficient mice with PC3 tumor xenograft. Sodium pyroglutamate isolated from Agaricus blazei has been shown to have potent antitumour and anti-metastatic actions. The data suggested that the broth of A. isolated from the lipid fraction of Agaricus blazei Murill has also been shown to have anti-tumour activity in Sarcoma 180-bearing mice.6-glucan complex with an average molecular weight of 20kDa. but also in the non-injected left flank.. blazei may directly inhibit the growth of prostate cancer cell via an apoptotic pathway and suppress prostate tumour growth via antiproliferative and antiangiogenic mechanisms (Yu et al. The efficacy and safety of Senseiro (containing extracts from Agaricus blazei Murill) and Rokkaku Reishi..

levels of immunosuppressive acidic protein (IAP) in mice receiving LM fractions. The data showed that the fraction from Agaricus blazei induced HL-60 cell apoptosis and that the combined effect of down-regulation of telomerase activity and up-regulation of mRNA expression of the caspase-3 gene could be the primary mechanism of induction of apoptosis. indicating the possible activation of granulocytes (Fujimiya et al. Lentinus edodes had no effect on the growth of either the primary or metastatic tumours (Ebina. Typical apoptotic characteristics were determined by morphological methods using DNA agarose gel electrophoresis and flow cytometry. particularly LM-3. Inhibitory effects of Agaricus blazei extracts on human myeloid leukemia cells NB-4 and K-562 cells have also been reported (Kim et al. A subsequent study from another group has also demonstrated the chemo-preventative potential of an Agaricus blazei (Ab) Murrill mushroom meal in a medium-term rat liver 165 . An immuno-suppresive acidic protein (IAP) was induced by both the Agaricus and Himematsutake preparations but not by Lentinus edodes. 1999). which was associated with the arrest of G2/M phase and the induction of apoptotic cell death via caspase-3 activation (Jin et al. 2006). An extract from fruit bodies of Agaricus blazei has been evaluated in a "double grafted tumour system" mouse model and reported to cure the primary tumour and inhibit the growth of metastatic tumours in this model. 2007). An aqueous extract of Agaricus blazei has been shown to exert a hepato-protective effect on both liver toxicity and hepato-carcinogenesis on rat liver toxicity induced by different doses of diethylnitrosamine (Barbisan et al.. The effect of an RNA-protein complex isolated from A. blazei Murill. A separate extract from Agaricus blazei (Himematsutake) inhibited the growth of the primary tumour. It was found that an Agaricus blazei extract could inhibit cell growth in a dose-dependent manner. These findings provide good evidence that the isolated fraction may be of value for the clinical treatment of acute leukemia (Gao et al.. 2002). significantly increased.... on human leukemia HL-60 cells has been studied. 2007). A subsequent study by the same group has shown a similar effect on apoptosis by Agaricus blazei on human leukemic U937 cells via similar mechanisms (regulation of Bcl-2 and caspase-3) (Jin et al. Induction of apoptosis in human gastric epithelial AGS cancer cells by an aqueous extract of Agaricus blazei has been demonstrated. 2009a).. 2005).

2003)... The lack of an antibiotic effect on pneumococci in vitro and increased levels of cytokines MIP-2 and TNF in the serum of mice receiving AbM extract. indicated that the protective effect of AbM was due to the involvement of the native immune system. The data indicated that previous treatment with the highest concentration of Agaricus blazei (11. Anti-bacterial effects of Agaricus blazei Murill (AbM) have been investigated. Bacterial septicemia can occur during gastroenterological surgery. the same group reported that treatment with aqueous extracts of Agaricus blazei does not exert a protective effect against the development of GST-Ppositive foci induced by DEN (Barbisan et al. Chemo-preventative activity of the mushroom meal was observed for the Ab 29 (OB and CB) and Ab 26 (CB) strains in terms of the number of putative pre-neoplastic altered foci of hepatocytes which express either the enzyme glutathione S-transferase. This was associated with inhibition of foci cell proliferation in the animals fed the Ab 29 (OB) and Ab 26 (CB) strains. The putatively anti-infective 166 . The anti-infection properties of AbM have therefore been shown in vivo and the results suggest that AbM extract may be useful as an additional prophylactic and possibly therapeutic treatment against bacterial infections in humans (Bernardshaw et al. The AbM extract protected against systemic Streptococcus pneumoniae 6B infection in mice and was most effective when given 24h before inoculation but it also had protective effects when given together with challenge compared with control. indicating a protective effect against DEN-induced liver cytotoxicity/genotoxicity (Barbisan et al. mixed at a level of 10% in a basal diet. The results suggest that the protective influence of the Ab meal against the DEN potential for rat liver carcinogenicity depends on both the strain and period of mushroom harvest (Pinheiro et al.) were fed during a 6-week period with dry powdered mushroom strains Ab 29 or 26. placental form (GST-P+) or the transforming growth factor-alpha.carcinogenesis assay. 2003b). The effects of crude extracts of the mushroom Agaricus blazei Murrill (Agaricaceae) on both DNA damage and placental form glutathione S-transferase (GST-P)-positive liver foci induced by diethylnitrosamine (DEN) have also been investigated in adult male Wistar rats.5mg/ml) significantly reduced DNA damage. each one with opened (OB) or closed basidiocarp (CB). Male Wistar rats initiated for hepatocarcinogenesis with diethylnitrosamine (DEN. 2005a).. A subsequent study by the same group has shown that an extract of Agaricus blazei Murill can protect against lethal septicemia in a mouse model of faecal peritonitis. 2003a) while in a subsequent study. and for the Ab 29 (OB) and Ab 26 (CB) strains on the size of GST-P+ foci. 200mg/kg i.p.

The mice were orally given an extract of AbM or phosphate-buffered saline 1 day before the induction of peritonitis with various concentrations of faeces from the mice. is applicable for the preparation of protein-bound polysaccharide powders with higher antitumour activities from Agaricus Blazei Murill (Hong et al.. or absolute or relative organ weights in control or treatment groups. and Boletus edulis have been shown to have significant antioxidant properties. Long-term (2 years) feeding of rats of a powdered diet containing Agaricus blazei at levels up to 25. 2007). 2006).1-diphenyl-2-picrylhydrazyl radicals whereas hot water extracts were more effective in reducing power. 2001). 2004). body weight gain. Mortality in male treatment (mushroom) groups was significantly lower than in controls. as measured by the number of colony-forming units of bacteria in blood. Mice that were orally treated with Agaricus blazei Murill extract before bacterial challenge showed significantly lower levels of septicemia and improved survival rates (Bernardshaw et al.. Histopathological studies showed no increased incidence of tumours. and the survival rate of the animals were compared between the groups. The ethanolic extracts were more effective than hot water extracts in antioxidant activity using the conjugated diene method and scavenging ability on 1. Thermostable antioxidant activity has also been reported from Agaricus blazei Murill (Izawa and Inoue... A study to evaluate the chronic toxicity and oncogenicity of Agaricus blazei Murill in F344 rats has recently been reported (Lee et al. A recent study has demonstrated that ultrafiltration. Naturally occurring antioxidant components including total tocopherols (3. scavenging ability on hydroxyl radials and chelating ability on ferrous ions as demonstrated by their lower EC50 values. 2007).18- 167 . A study has also reported good bioavailablity of both copper and zinc from mycelium of Agaricus blazei Murrill equating to very good levels of recommended daily intakes of these minerals from small amounts of (1g) of this mushroom (Rabinovich et al. Agrocybe cylindracea. Ethanol extracts and hot water extracts of Agaricus blazei.000 ppm (parts per million) revealed no remarkable change in mean body weight. The state of septicemia.immunomodulatory action of Agaricus blazei Murill (AbM) has been studied in an experimental peritonitis model in BALB/c mice. 2008). in combination with spray-drying.. hematologic or serum chemistry parameters. Anti-viral activities of Agaricus blazei Murill have been demonstrated against cytopathic effects induced by western equine encephalitis (WEE) virus by the mycelial fractions but not those of fruiting bodies (Sorimachi et al.

and glycemia were similar between the control and supplemented groups. blazei cultured on the top shoot of sugar cane medium has increased pharmacological activity compared to mushrooms cultured on rice or wheat straw or broad leaf bark (Yoshimoto et al. To evaluate leukocyte homing and activation. Blazei-treated group. Agaricus blazei mushrooms were prepared on culture media composed of 1) tops of sugar cane shoots (stems and leaves). Analysis of the spleen showed higher levels of activation of neutrophils.67-5. mice were injected with radiolabeled leukocytes. 2) rice straw 3) wheat straw. blazei cultured on the top shoot of sugar cane medium showed the most effective results compared with that cultured on other media. A.. The pharmacological effects of this mushroom were examined by the following methods. Using apolipoprotein E-deficient (ApoE(-/-)) mice. weight gain. Blazei-treated group. The A. NKT cells. 2010). An aqueous extract of Agaricus blazei Muril administered daily starting 40 days after the onset of streptozotocin-induced diabetes in Wistar rats assisted in the recovery of pulmonary tissue of the rats.. and 5) used substrate after Pleurotus ostreatus cultivation.81mg/g) were found in the extracts and their contents were associated with the EC50 value of the antioxidant properties (Tsai et al. Circulating NKT cells and monocytes were also more activated in the supplemented group. followed by a reduction in the A. Blazei treatment effectively reduced the oxidative stress and contributed to tissue recovery (Di Naso et al. The results suggested that the A. blood lipid profile. the effects of supplementation of mice with Agaricus blazei for 6 or 12 weeks has been studied on the activation of immune cells in the spleen and blood and on the development of atherosclerosis. an experimental model of atherosclerosis. 2007).6. blazei-supplemented animals. and monocytes as well as increased production of TNF-alpha and IFN-gamma. Differences of the pharmacological effects of Agaricus blazei cultured on various materials have been examined. Food intake. Pulmonary lipoperoxidation increased in the diabetic animals compared to the control group. 4) broad leaf tree bark. In both the anti-platelet aggregation test and chemokine gene revelation control test. 3) improvements of rough surfaces by using replica method. 2) inhibition of IL-8 gene expression stimulated by TNF-alpha. 1) anti platelet aggregation stimulated by PAF or arachidonic acid Na. Atherosclerotic lesion areas were larger in the aorta of supplemented mice and 168 .18mg/g) and total phenols (5. 2005).. which showed enhanced leukocyte migration to the spleen and heart of A. The pulmonary tissue in diabetic rats showed oxidative alterations related to the streptozotocin treatment. iNOS was increased in the lung in diabetic rats and reduced in the A.

simultaneous and pre-treatment+continuous. 2011).exhibited increased numbers of macrophages and neutrophils and a thinner fibrous cap. increased the survival of rat cardiomyocytes (H9c2 cell line) without cytotoxicity. TLR4). post-treatment and pre-treatment+continuous conditions. the tumor mass appeared to grow more slowly following ABM doses of 4. has shown that A. Agaricus Blazei Murill (ABM) extract.. Reactive oxygen free radicals have been reported to be important in ischemia-reperfusion injury cascades. carried out under pre-treatment. The effects of an extract of Agaricus blazei Murrill (ABM) has been evaluated on HT-29 human colon cancer cells in severe combined immunodeficiency (SCID) mice. since this mushroom was demonstrated to have a preventive effect against pre-neoplastic colorectal lesions evaluated by the aberrant crypt foci assay (Ishii et al. Supplementation caused an increase in the number of monocytes and in phagocytic activity. consequently increasing phagocytic capacity especially in the groups pre-treatment. blazei enhanced local and systemic inflammation. Oral administration of ABM (up to 45 mg ABM daily for 6 weeks) did not prevent tumor growth.. upregulating pro-inflammatory molecules.. ABM-pretreated rats that underwent myocardial ischemia-reperfusion had greatly reduced infarct areas compared to those in the control group. and plaque vulnerability (MMP9) were seen after 12 weeks of supplementation. Pretreatment with ABM extract reduced hydrogen peroxide-induced cell damage and increased cell survival. Supplementation with Agaricus blazei. ABM may have a cardioprotective effect by increasing antioxidant activity. 169 . previously reported to modulate oxidative stress. suggesting that supplementation increases a proliferation of monocytes. The data suggest that A. but compared with the control group (0 mg ABM). and enhancing leukocyte homing to atherosclerosis sites without affecting the lipoprotein profile (Goncalves et al. 2010a).5 and 45 mg) (Wu et al. blazei has proatherogenic repercussions.. A. blazei did not have genotoxic activity but showed antigenotoxic activity (Comet assay). which greatly ameliorates myocardial injuries caused by myocardial ischemia-reperfusion injuries (Huang et al. leukocyte adhesion (VCAM-1). 2011b). simultaneous treatment. A. blazei-induced transcriptional upregulation of molecules linked to macrophage activation (CD36. The data show that the immunostimulatory effect of A. 2011). neutrophil chemotaxy (CXCL1). blazei could promote immunomodulation which can account for the destruction of cells with DNA alterations that correlate with the development of cancer.

also known as the sun mushroom. is native to Southeastern Brazil. The test substances showed anti-viral activity and were more effective when added during the poliovirus infection. The immunomodulatory effects of Agaricus blazei Murill and resultant impacts on an array of health outcomes have recently been reviewed (Hetland et al. just after the virus inoculation (time 0 h). PLS and EtOHE were added. 2011. 2011). 170 .. there was a concentration-dependent reduction in the number of plaques by up to 50%. brasiliensis have been evaluated for anti-viral activity against poliovirus type 1 in HEp-2 cells.. 67% and 88%. The evaluation of the time of addition by plaque assay showed that when AqE.7 mg/ml) of Agaricus brasiliensis Mural (ABM) caused morphological changes and significantly reduced viability of human oral cancer CAL 27 Cells after 48 h of treatment. and is widely consumed. These findings suggest that Agaricus blazei Murill. mainly in the form of tea..Mechanistic studies of apoptosis in human hepatocellular carcinoma cells have shown that Agaricus blazei Murill is able to act as an enhancer to sensitize doxorubicin (Dox)mediated apoptotic signaling. the authors suggested that they may act at the initial stage of the replication of poliovirus (Faccin et al.9 mg/ml) and hot water extracts (0. and this sensitization can be achieved by enhancing intracellular Dox accumulation via the inhibition of NFkappaB activity. Agaricus brasiliensis (previously named Agaricus blazei ss. when combined with low doses of Dox. Lima et al. may have the potential to provide more efficient therapeutic effects against drug-resistant human hepatocellular carcinoma (Lee and Hong. Agaricus brasiliensis Ethanol extracts (0. Both extracts were able to induce apoptotic cell death in CAL 27 cells via the release of cytochrome c from mitochondria into the cytoplasm and activation of caspase-3 in vitro (Fan et al. respectively. Aqueous (AqE) and ethanol (EtOHE) extracts and an isolated polysaccharide (PLS) from the fruiting body of A.. As the extracts had little effect on reducing viral adsorption and did not show any virucidal effect. 2011). Heinem). 2007). 2011).

brasiliensis 171 . The fruiting body extracts were more effective in the DPPH radical scavenging activity and lipid peroxidation inhibition than the mycelia extracts. oxalic. and ammonium oxalateinsoluble fractions isolated from the fruiting bodies of Agaricus brasiliensis into C3H/HeN mice has been shown to play an important role in the maintenance of hematopoietic cells for compromised patients at the risk of infection associated with malignancy (Fujimiya et al. Furthermore.19% inhibition compared to a control group.Studies with an aqueous extract of Agaricus brasiliensis S. The results strongly suggest that the pharmacological action of the cold water extract of A. 2/5 (HWE). 2006). reaching 72. citric. The mycelium polysaccharide and exo-polysaccharide (EPS) of Agaricus brasiliensis LPB 03 produced by submerged fermentation has shown strong inhibition against Sarcoma 180 in mice.) failed to show any anti-microbial effects against Salmonella enterica serovar Typhimurium (Fantuzzi et al. The administration of ethanol-soluble. boiling water-soluble. 2010). fumaric and trans-aconitic acids). brasiliensis is significantly stronger than that of the hot water extract (Furukawa et al... All extracts possessed antioxidant properties.. urinary glucose exclusion. The mycelia extracts however were more effective in the ABTS radical scavenging activity and ferrous ion chelating ability (Carvajal et al. The structure and anti-tumour activity of polysaccharide fractions of the fruit body of Agaricus brasiliensis have been studied in cold and hot water extracts (CWE and HWE) on a mouse diabetic model (C57BL Ksj-db/db). Wasser et al. Phenolic compounds present in mushroom extracts from A.. and 0/5 (CWE) suggested the activity of the renal protection in the cold water extract. Determination of the phenolic and organic acid contents of Agaricus brasiliensis as well as the antioxidant activities of its fruiting bodies and its mycelia obtained from submerged cultivation has shown the presence of 3 phenolic compounds (gallic acid. and organs weight were comparable. Compared to the water administered control group. 2006).. urinary pH. By megascopic and microscopic examinations of renal sections. 2007). The splenocytes of CWE administered mice produced a higher concentration of interleukin-6. (=Agaricus blazei Murrill sensu Heinem. syringic acid and pyrogallol) and 8 organic acids( benzoic. alpha-ketoglutaric. acetic. malic. the number of the mice having abnormal kidney was 3/5 (control). 2012).. 50% of mice in the test group demonstrated total tumour regression (Fan et al. 2011) nor on immunomodulatory properties (Fantuzzi et al. blood glucose level. the body weight.

total cholesterol (p = 0. An Agaricus brasiliensis-derived cold water extract has also been reported to have some water-soluble toll-like receptor ligand complexes and induce cytokine production via a tolllike receptor 2-dependent mechanism (Yamanaka et al. aspartate aminotransferase (p = 0.01). flatus retention. placebo-controlled clinical trial carried out in Brazil over a six month period with 56 patients has studied life quality of postsurgical patients with colorectal cancer after supplementation of the diet with Agaricus sylvaticus (30 mg/kg/day).04). the supplemented group had increased physical activity.05). 2008). A further evaluation of the same patients reported that the Agaricus sylvaticus group had significantly reduced fasting plasma glucose (p = 0. 2011). systolic blood pressure (p = 0. double-blind. alternate diarrhea/constipation. 2011). all effects that were not observed in the placebo group.0001).02). The data suggest that dietary supplementation with Agaricus sylvaticus was capable of providing metabolic benefits to the biochemical. pyrosis.0001)and diastolic blood pressure (p = 0. IgM (p = 0. 172 . postprandial fullness. flatulence. Agaricus sylvaticus A randomized. alanine aminotransferase (p = 0.05). 2010). improved disposition and mood. creatinine (p = 0..strongly generated reactive oxygen species (suggesting immunomodulatory effects) in human PBMCs and K 562 cells in vitro (Wei et al. reduced constipation. abdominal distention and abdominal pain. nausea. reduced complaints of pain and reduced alterations of sleep such as insomnia and restless sleep.02). enzymatic and blood pressure parameters of these patients with colorectal cancer in the postsurgical phase (Fortes and Novaes.. diarrhea. After six months of treatment. IgA (p = 0.. The supplemented group also presented with increased appetite. indicators which were not observed in the placebo group (Fortes et al.0001).

.. An investigation of bioactivity gave positive results for ceramide. It has been reported that this lectin is a member of the galectin family and the dimeric form is the active unit for functional performance..2'-azinobis-(3ethylbenzthiazoline-6-sulphonic acid) radical cation (ABTS(+)) and inhibition of lipid peroxidation of rat brain homogenate. Significant correlation was found between the total phenolic content and the antioxidant activity in the EA fraction and its sub-fractions (Lo and Cheung. The recombinant lectin showed comparable tumour cell apoptosis-inducing activity with the wild lectin but no DNase activity (Yang et al.. Hypsizigus mamoreus. as well as possibly reducing the development of the above cancers (Diyabalanage et al. Chiodini) Agrocybe aegerita is an edible mushroom with reported anti-tumour properties. 2009). Yang et al. 2008). has been evaluated by scavenging activity of 2. which showed the most potent antioxidant activity in the above two assays. Piopinno. breast and central nervous system cancer cell lines suggesting that the compound may be useful in alleviating inflammatory conditions. Ceramide inhibited the cyclooxygenase (COX) enzymes. The ethyl acetate (EA) fraction. COX-1 and -2 and its anti-cancer potential was investigated against five human cancer cell lines in vitro and it was found to inhibit the proliferation of stomach. 173 . A lectin from Agrocybe aegerita (AAL) has been found to possess potent tumoursuppressing function and tumour cell apoptosis-inducing activity. Agrocybe aegerita and Flammulina velutipes (Ou et al. methyl-beta-Dglucopyranoside and alpha-Dglucopyranoside.Agrocybe aegerite (Black Poplar. 2005). 2005). was further fractionated by a Sephadex LH-20 column into four subfractions (EA1-EA4). 2005. Antioxidant activity of a methanol crude extract and its fractions. Proliferation of human leukemic U937 cells has been shown to be significantly inhibited by conditioned medium of human peripheral blood mononuclear cells stimulated with coldwater extracts (10-800 µg/mL of medium) of dietary mushrooms. Its full sequence has been published. along with linoleic acid and its methyl ester. from the fruiting bodies of Agrocybe aegerita.

topical application of the polysaccharide resulted in marked inhibition of 12-O-tetradecanoylphorbol 13acetate (TPA)-induced ear edema in mice. Furthermore. no abnormal changes were observed in clinical signs.7 cells. All animals survived to the end of the study. No significant differences were found in urinalysis. hematology and serum biochemistry parameters between the treatment and control groups. 174 . During the experiment period. The no-observed-adverse-effect level (NOAEL) of Antrodia cinnamomea was identified to be greater than 3000 mg/kg BW/day (the highest dose tested in this study) in Sprague-Dawley rats (Chen Tai et al. Osteoclast forming suppressive compounds (important in osteoporosis) have been isolated from the mushroom Agrocybe chaxingu (Abel et al. Agrocybe chaxingu A beta-glucan from Agrocybe chaxingu significantly inhibited lipopolysaccaride (LPS)-induced nitric oxide (NO) and cyclooxygenase-2 (COX-2) expression levels in murine macrophage Raw 264. 2009a). and to exert an anti-hepatoma effect in vivo via inhibition of tumor growth and extending the survival time of tumor bearing mice (Jiang et al. 2007).and COX-2-related disorders such as inflammation (Lee et al.. a medicinal mushroom has been recently completed in 80 Sprague-Dawley rats. leading to induced cell apoptosis in vitro.. Antrodia cinnamomea A 90-day sub-chronic oral toxicological assessment of Antrodia cinnamomea. Necropsy and histopathological examination indicated no treatment-related changes. These results suggest that this polysaccharide may be useful for the treatment of NO. Doses of 3000. body weight and ophthalmological examinations. 2200 and 1500 mg/kg BW/day were given for 90 consecutive days and reverse osmosis water was used as control. 2012)..A lectin isolated from Agrocybe aegerita has been shown to bind to the surface of hepatoma cells..

. 2004). In patients with functional constipation. 2004b). glucuronic acid and xylose but no sulfate esters.. The specific anti-coagulant activity of the purified polysaccharide was 2 international units (IU)/mg and its average mass was approximately 160kDa. Auricularia auricular (Wood Ear) In vitro evaluation of antioxidant activities of Auricularia auricular has shown significant inhibition of lipid peroxidation. auricula represented 403. The IC50 value of crude. An acidic polysaccharide with anti-coagulant activity has been isolated from Auricularia auricula using water. fiber supplements using ear mushrooms has been shown to significantly improve constipation related symptoms without serious side effects (Kim et al..2011a). Ear mushrooms (Auricularia) are known to have higher fiber contents (by ~50%) than other mushroom varieties. 2011b). possibly via their significant antioxidant activity (Wu et al. A further toxicological study on this mushroom in pregnant Sprague Dawley rats concluded that this mushroom has no teratogenic effects in female rats (Chen Tai et al. 510. The polysaccharide from this species of mushroom contains mainly mannose. and potent hydroxyl radical scavenging activity when compared with the drug catechin.. and 373mg/ml respectively of hydroxyl radical scavenging activity and 310. Its anti-coagulant activity was due to catalysis of thrombin inhibition by anti- 175 . boiled and ethanolic extracts of A. 191 and 850pmole/mg dry wt/h respectively) over the control (Acharya et al. glucose. alkali or acid extracts. 572 and 398mg/ml respectively of lipid peroxidation. The alkali extract showed the highest anticoagulant activity and was further purified using gel filtration chromatography. Auricularia auricular has been shown to have hypocholesterolemic properties (Cheung. 2010). 1996b). Auricularia auricula polysaccharides have also recently been reported to have a positive effect on heart function of aged mice. Constipation is one of the most prevalent gastrointestinal complaints and high fiber intake is recommended as an initial therapy for constipation. boiled and ethanolic extracts were shown to significantly increase nitric oxide production (664. while crude.

a well-known anti-platelet agent. An immunomodulatory protein (APP) has been purified from the fruiting body of an edible Jew's Ear mushroom. 2009b).7 macrophages. 2003). on thrombosis (Yoon et al. The glucuronic acid residues were essential for the anticoagulant action of the mushroom polysaccharide since the activity disappeared after reduction of its carboxyl groups.1% 2-mercaptoethanol. Although murine splenocytes are stimulated by the mitogen concanavalin A (ConA). 2004). The isolated fraction of polysaccharides enhanced phagocytosis of macrophages and stimulated nitric oxide (NO) release and cytokine secretion of macrophage in a dose-dependent manner. The authors suggested that polysaccharides from these mushrooms may constitute a new source of compounds with action on coagulation. The fraction also augmented mRNA transcription of inducible nitric oxide synthase (iNOS). Auricularia polytricha (Jew's Ear) The isolation of an anti-tumour polysaccharide from Auricularia Polytricha and its effects on macrophage activation has recently been reported (Yu et al. as with aspirin. followed by ammonium sulfate fractionation. The data suggest that this protein isolated from Auricularia polytricha is an immune stimulant (Sheu et al.4kDa and its pI is approximately 5. 176 . APP suppressed their proliferation in a dose-dependent manner.. tumour necrosis factor (TNF)-alpha. markedly increasing their proliferation and gamma-interferon (IFN-gamma) secretion..thrombin. APP is a simple protein without carbohydrate. interleukin (IL)-1 beta and IL-6 and increased the protein expression of inducible nitric oxide synthase. and presented no cytotoxicity in vitro. Auricularia polytricha. APP alone activates murine splenocytes. DE-52 and P. In ex vivo tests using rats orally fed with the polysaccharide.1. APP also enhanced the production of both nitric oxide (NO) and tumour necrosis factoralpha (TNF-alpha) by LPS-induced RAW 264. by extraction using 5% cold acetic acid in the presence of 0. Inhibition of Factor Xa by anti-thrombin was not catalyzed by the polysaccharide.. but not by heparin cofactor II. and can agglutinate mouse red blood cells. perhaps. The molecular mass of APP was around 13.MonoQ anion-exchange chromatography. platelet aggregation and. an inhibitory effect on platelet aggregation was observed.

Cordyceps militaris An extract of Cordyceps militaris has been shown to suppress dextran sodium sulphate (DSS)induced acute colitis in mice and production of inflammatory mediators from macrophages and mast cells. The extract significantly attenuated DSS-induced body weight loss. and infiltration of inflammatory cells induced by DSS.Coprinus comatus Altered androgen receptor (AR) activity caused by point mutations or signalling mechanisms that regulate AR function has been proposed as a key mechanism in the transition to the androgen-independent stage of prostate cancer. gross bleedingand. The pharmaceutical value of the Basidiomycota fungi Coprinus comatus has also been reviewed by the same group (Dotan et al. It has been demonstrated that a hexane extract prepared from Coprinus comatus ( C. 2011b). comatus) strain 734 was able to reduce AR levels and prostate-specific antigen gene expression in the LNCaP-treated cell line (Dotan et al. 2010). and suppressed epithelial damage. the extract inhibited iNOS and TNF-alpha mRNA expression in colon tissue of DSS-induced colitis and in RAW264. 2011a). In addition... loss of crypts. 177 . 2011).. Cordyceps militaris extract suppressed degranulation of mast cells in the colon of mice with DSS-induced colitis and in antigen-stimulated mast cells. diarrhea.. One of these fractions (F-32) also inhibited the proliferation and clonigenicity of LNCaP cells and inhibited the binding of AR to the PSA enhancer region and inhibited Akt-mediated AR phosphorylation at Ser 213 (Dotan et al. prevented shortening of colon length and crypt length.7 cells. A further study from the same group isolated 2 fractions from the same mushroom strain that inhibited AR-mediated reporter activity and reduced the levels of AR and prostate-specific antigen (PSA) transcripts in LNCaP cells. The data suggest that the extract from Cordyceps militaris has anti-inflammatory activity in DSSinduced acute colitis by down-regulating production and expression of inflammatory mediators (Han et al. loss of goblet cells.

stimulate hemopoietic function. 2010). has been hypothesized as a possible treatment approach to both diabetes and depression. sinensis having an antidepressant-like activity... The extract was able to alleviate the chronic allergic inflammation by increasing the level of interleukin-10. Cordyceps sinensis (Caterpillar mushroom) A Cordycep extract has recently been evaluated in asthmatic children during remission stage (Sun et al.. Vanadium-enriched Cordyceps sinensis (VECS).Adenosine. However.. 2012b). and being able to attenuate a diabetes-induced increase in blood glucose concentrations (Guo et al. 2011). which is due to the inhibition of inflammation and increase of antioxidants activity related to lesion pathogenesis (Wang et al. While there was no significant difference in graft survival rate or occurrence of reject reaction. 178 . as well as reduce the incidence of infection and the dosage of the drugs cyclosporine A and tacrolimus used. 2010. The synergistic effects of Cordyceps sinensis with the drug cyclosporine A in preventing allograft rejection was recently reported in rats (Ding et al. 2009b). The Cordyceps extract inhibited the proliferation and differentiation of Th2 cells and reduced the expression of related cytokines by down-regulating the expression of GATA-3 mRNA and up-regulating the expression of Foxp3 mRNA in peripheral blood mononuclear cells. 2009a) but a retrospectively study by the same group has evaluated the immunoregulatory effect of a dry powder preparation of Cordyceps sinensis mycelia on humans after renal transplantation (Ding et al. the hypothesis remains to be proven. 2011b). iso-sinensetin and dimethylguanosine from fruiting bodies of Cordyceps militaris have been shown to have antioxidant and HIV-1 protease inhibiting activities (Jiang et al. and therefore. Cordymin. based on vanadium compounds having an ability to imitate the action of insulin and C. treatment did effectively protect liver and kidney... improve hypoproteinemia. Guo et al. it may be useful for immunoregulation after organ transplantation. a peptide purified from Cordyceps sinensis has been reported to have a neuroprotective effect in the ischemic brain..

-7. had the most potent effect against all four cancer cell lines. The EtOAc extract contained carbohydrates. with IC50 values between 12mg/ml (on B16) and 45mg/ml (on MCF7). with IC50 values below 132 mg/ml. +7 and +10 days after the tumour transplantation augmented the activity about four times greater than that of the control. and ethanol (EtOH) showed a significant and dosedependent inhibitory effect on the proliferation of four cancer cell lines. the EtOAc extract showed a significant inhibiting effect on B16-induced melanoma in C57BL/6 mice. partly via the induction of cytokines (Cheung et al. The tumour-bearing mice receiving this extract lived significantly longer than the other groups without CSE (Yamaguchi et al. These effects also reportedly attenuated the severity of lupus in these mice (Chen et al. 2009). An extract of Cordyceps sinensis (CSE) has been tested in C57BL/6 mice implanted subcutaneously with syngeneic EL-4 lymphoma cells. sequentially extracted by petroleum ether (PE). chemotaxis was dramatically depressed within a few days after EL-4 transplantation up to the end of life. A polysaccharide isolated from cultured Cordyceps sinensis (named cordysinocan). ethyl acetate (EtOAc). Phagocytic activity of macrophages was also decreased in tumour-bearing mice treated with cyclophosphamide (100mg/kg) 3 and 5 days after tumour transplantation. In contrast.. HL-60 human pre-myelocytic leukemia and HepG2 human hepatocellular carcinoma.. The EtOAc extract. 2007b). 2005).An exo-polysaccharide fraction from cultivated Cordyceps sinensis has been shown to have immunomodulatory and anti-tumour effects on (B16 melanoma) tumour-bearing mice (Zhang et al. 179 . In an animal test. but administration of CSE restored the activity to more than the normal level.. Cultivated mycelium of Cordyceps sinensis. of which ergosterol and related compounds were identified as a major class of active constituents contributing to the in vitro cytotoxicity. it had much lower cytotoxicity against normal mouse bone marrow cells.. The overall efficacy of CSE was tested with protective activity against systemic infection by Salmonella enteritides. in particular. adenosine. B16 mouse melanoma. has also been reported to activate immune responses in cultured T-lymphocytes and macrophages. -4. Cordyceps sinensis has also been shown to possess immunopotentiating effects in lupus-prone autoimmune (NZB/NZW) mice via action on peripheral mononuclear T lymphocytes. ergosterol and a trace amount of cordycepin.. 2009). causing a 60% decrease of tumour size over 27 days (Wu et al. Oral administration of the extract led to a reduction of tumour size and prolongation of the host survival time. +4. As for the activities of peritoneal macrophages. A hot water extract failed to show such activity. MCF-7 breast cancer. but treatment with CSE at -14.

velutipes with higher phenolics content showed more efficient antioxidant capacity against lipid oxidation. 2009).. In mice fed a cholesterol-free diet and those fed a cholesterol-enriched diet..7R. HW also increased the high-density lipoprotein (HDL) cholesterol level. 2003). whereas extracts prepared from the spent culture medium of F. 2010b). Oral administration of FVE displayed anti-tumor activity through activating both innate and adaptive immunity of the host to prime a cytotoxic immune response and IFN-gamma played a key role in the anti-tumor efficacy of FVE (Chang et al. significantly increased the life span and inhibited the tumor size of BNL 1MEA. The amount of 180 . respectively) with the cholesterolenriched diet decreased more than in the control group. Extracts prepared from the fruiting body of Flammulina velutipes with a high ergothioneine content exhibited a stronger delay of the autoxidation activity of oxymyoglobin. The changes in HDL-and VLDL+LDLcholesterol levels consequently decreased the atherogenic value. but decreased the very low-density lipoprotein plus low-density lipoprotein (VLDL+LDL) cholesterol level.1990). The serum total cholesterol (TC) of all mice groups administered HW (150 and 300mg/kg/d. The 300mg/kg dose had a significant effect on the serum total cholesterol level (Koh et al. Flammulina velutipes (Enoki) Oral administration of 10mg/kg of an immunomodulatory protein (termed FVE) purified from Enoki mushroom (Flammulina velutipes) and known as an activator for human T lymphocytes. body and liver weights were not significantly different from those of the controls. Dried powder of cultured Cordyceps sinensis mycelium has also shown cytotoxic effects towards promyelocytic leukemia HL-60 cells via a suggested dependency on sterol constituents and the activation of caspases-3/7 (Matsuda et al. The results indicated that HW in rats administered a cholesterol-enriched diet decreased the plasma cholesterol level. A study has been conducted to investigate a hypocholesterolemic effect of a hot-water fraction (HW) from cultured mycelia of Cordyceps sinensis.. Among the mice fed the cholesterol-enriched diet.1 (BNL) hepatoma-bearing mice.

1982). ex Fr. and significant inhibition of MCF-7 tumour colony formation in vitro. regardless of the hormone receptor status of the cancer cells. Coprinus comatus and Flammulina velutipes (CME. CCE and FVE.3%. D-galactose 17. It has been reported that there is currently no effective therapy for malignant estrogenindependent breast cancer.. isolated from the culture mycelium of Flammulina velutipes (Curt. These results suggest that the inedible parts and spent culture medium of F.3%. ex FR. respectively). velutipes was fractionated and among the polysaccharides isolated. 2010).breast cancer cells. An anti-tumour polysaccharide. D-xylose 6.) SING. Another anti-tumour polysaccharide (EA5) also isolated from F.human breast cancer (Gu and Leonard. and Flammulina velutipes contain potent anti-tumour compounds for breast cancer.. The anti-tumour activities included marked growth inhibition of both ER+ and ER. induction of rapid apoptosis on both ER+ and ER. velutipes could potentially be considered as a readily available source of natural antioxidants (Bao et al. the highest molecular weight polysaccharide (EA501) showed the highest anti-tumour activity..ergothioneine was distributed highest in the inedible (base and mycelium) parts of the mushroom.) Sing. The component sugars of EA501 were found to be D-glucose 42. EA3 isolated from Flammulina velutipes (CURT. MCF-7 tumour colony formation rate was reduced by 60% in CCE. 2006). Water-based extracts of three mushroom species. and has a molecular 181 . BT-20) breast cancer cells has been undertaken to select potential agents with broad-spectrum anti-tumour activity against breast cancer cells. The degree of produced cytotoxicity on ERbreast cancer cells was very high.cells. Coprinellus sp. Screening of 38 species of edible mushrooms on human estrogen-receptor positive (ER+) (MCF-7) and estrogen-receptor negative (ER-) (MDAMB-231. The anti-proliferative and cytotoxic activities of the three mushroom extracts were dose-dependent. is a weakly acidic glycoprotein containing more than 90% protein and less than 10% carbohydrate. This finding is important due to the lack of chemotherapeutic and chemo-preventive agents for ER.2%. has been shown to be composed of D-glucose with the chemical structure of a beta-(1 leads to 3)-glucan. have been identified as anti-breast cancer agents.and CME-treated cells and nearly completely inhibited (99%) by FVE treatment. Mushroom extracts CME and FVE induced a rapid (within 5 hours) apoptosis on MCF-7 and MDA-MB-231 cells.7% and L-arabinose 14. D-mannose 12. A further study by the same group has shown that proflamin. These results suggest that the mushroom species Coprinus comatus.7% (Ikekawa et al. Coprinellus sp.

Omphalotus olearius. When the ethanol extracts were tested.4% to 62. the highest AA were found in Agaricus nevoi. Proflamin exhibited no cytocidal effect against the cultured cell lines in vitro.. Water extracts from Coprinus comatus. 2007). Nutritional requirements for the production of ACE inhibitory activity from F. and ethyl acetate were used for extraction. velutipes were shown to include sucrose.1%. Plasma cholesterol concentration in rats has been shown to be reduced by feeding of mushroom Enokitake (Flammulina velutipes) fiber. and glutamic acid (Kim et 182 . ammonium acetate. B-16 melanoma (B-16) and adenocarcinoma 755 (Ca-755) in the mouse. Oral administration of proflamin produced no lethal or any other apparent adverse effect in mice (Ikekawa et al. The AA of ethanol extracts from Agrocybe aegerita and C. The results demonstrated that mushroom fiber lowered the serum total cholesterol level by enhancement of the hepatic low density lipoprotein (LDL) receptor mRNA (Fukushima et al. More recent studies by the same group have shown that Oral administration of proflamin significantly intensified various immunoresponses in tumour-bearing mice. 2007a)..7% and from 2. respectively. respectively.000Da. Oral administration of a protein from Flammulina velutipes has also been shown to possess anti-tumor activity in mice through activation of both innate and adaptive immunity of the host to prime a cytotoxic immune response with interferon-gamma having an effect on the anti-tumor efficacy of the protein (Chang et al. 2001). comatus increased from 46.. when the concentration of the extract increased from 2mg/ml to 4-8mg/ml with the authors suggesting that the extracts could be suitable as antioxidative agents and bioproducts (Asatiani et al. Proflamin has been shown to be markedly effective against the syngeneic tumours. water (culture liquid). but it was not very effective against the immunity of healthy (non-tumour-bearing) mice (Maruyama and Ikekawa. and Flammulina velutipes (Enoki) showed high antioxidant activities (AA) at 2mg/ml..weight of ~13. The increases in median survival time of treated mice with B-16 and Ca-755 were 86% and 84%. Agaricus nevoi.6% to 82. 1985). 2010a). Antioxidant activity of submerged cultured mycelium extracts of higher Basidiomycetes mushrooms has recently been reported. Three solvents ethanol. Antioxidant properties were studied from 28 submerged cultivated mycelium Basidiomycetes strains of 25 species. Angiotensin-converting enzyme (ACE) inhibitory activity (which has an effect on blood pressure reduction) has been demonstrated in the culture broth from Flammulina velutipes (strain 414). and Auricularia auricula-judae extracts at a concentration of 2mg/ml.

. and gram-positive bacteria. have been isolated from culture medium of Flammulina velutipes (Enoki). Hypsizigus mamoreus. Two cuparene-type sesquiterpenes.. 2002). 2005). but no effects were observed in rats with normal blood pressure (Harada et al. Flammulina velutipes polysaccharides (100. 183 . Flammulina velutipes polysaccharides may regulate murine immune function through promoting the production of TNF-alpha. enokipodins C (1) and D (2). 50.. with the most marked increase on TNFalpha level. All the metabolites showed anti-microbial activity against the fungus Cladosporium herbarum. INF-gamma and IL-2 in the supernatants of splenocyte cultures.al. A single dose of gamma-aminobutyric acid (GABA) enriched Flammulina velutipes (Enokitake) powder (0. Agrocybe aegerite and Flammulina velutipes (Ou et al. 2001). and the amount of TNF-alpha in PEC cultures.9 mg GABA/kg) resulted in a significant lowering of systolic blood pressure ( by 30 mmHg) in spontaneously hypertensive rats (SHR). Polysaccharides from Flammulina velutipes have been shown to promote the metabolic activity of murine splenocytes and peritoneal exudate cells (PEC) and increase the amounts of TNF-alpha. 2009). Antioxidative activities of Flammulina velutipes extract have also been reported to be able to stabilize the fresh colour of tuna meat during ice storage (Bao et al. Bacillus subtilis and Staphylococcus aureus (Ishikawa et al. INF-gamma and IL-2 (Chang et al. 2009a). 2011)... 25 mg/kg) raised the serum levels of TNF-alpha and INF-gamma in Sarcoma-180 tumour-bearing mice.. Proliferation of human leukemic U937 cells has been shown to be significantly inhibited by conditioned medium of human peripheral blood mononuclear cells stimulated with coldwater extracts (10-800mg/mL of medium) of dietary mushrooms. along with enokipodins A (3) and B (4).

G. Plasma total antioxidant power and the effect on lymphocyte DNA damage and repair were assessed before and after each treatment of a single dose (3. chronic hepatitis B. 2010) . lucidum or water (control). Type II diabetes. A 6 month open-label study in 51 patients with prostate cancer that ingested either Senseiro. Treatment with Ganopoly for 12 weeks showed hypoglycemic activity and produced some anti-viral and liver protective effects in patients with chronic hepatitis B infection. Lingzhi) The antioxidant properties of Ganoderma lucidum (Lingzhi or Reishi) and its effects on DNA damage and repair in lymphocytes have been evaluated in a small cross-over human intervention study with 7 healthy adults. Patients with biochemical failure after radical treatment for non-metastasized prostate cancer were enrolled in this open-label study. the findings suggest that Ganopoly may have some pharmacological activities. The efficacy and safety of Senseiro (containing extracts from Agaricus blazei Murill) and Rokkaku Reishi.. 2005). The trials evaluated effects on cancer.3 g) of G.. However. A series of trials evaluating Ganoderma lucidum in several disease states have been carried out. 2010).Ganorderma Lucidum (Reishi. containing extracts from the Agaricus blazei Murill mushroom. lucidum have no effect on DNA resistance to oxidative stress or repair in vivo (Wachtel-Galor et al. but did not significantly affect the level or rate of repair in lymphocytic DNA suggesting that the bioavailable antioxidants absorbed from G. or Rokkaku Reishi.. lucidum caused an acute increase in plasma antioxidant power. (containing the Ganoderma lucidum mushroom) have been evaluated over 6 months in patients with prostate cancer in Japan (Yoshimura et al. Overall. and no significant anticancer effects were observed with the intake of these two mushroom supplements (Yoshimura et al. although clinical proof is lacking. containing the Ganoderma lucidum mushroom has reported no serious adverse effects. and neurasthenia. No partial response in terms of serum prostate-specific 184 .. 2010). the same treatment regimen did not result in any objective response in late-stage cancer patients (Zhou et al. coronary heart disease.

No changes were observed with respect to quality of life scores. it has also been suggested that the stipes of fruiting bodies of Ganoderma species should be included in the preparation of extracts of these fungi in order to obtain the most comprehensive active 185 . Secondary outcome measures included changes in prostate size. G. prostate volume. peak urinary flow..1 points decreasing at the end of treatment. mean urinary flow. 2004a). placebo-controlled. 2008a). and dose-ranging study has been carried out in men with lower urinary tract symptoms (LUTS) to evaluate the safety and efficacy of an extract of Ganoderma lucidum that shows the strongest 5-alpha-reductase inhibitory activity among the extracts of 19 edible and medicinal mushrooms.. Serious adverse effects were not observed and no significant anticancer effects were observed with the intake of these two mushrooms in the study population. and the reported adverse effects. sinense. residual urinary volume after voiding. 2006). Overall treatment was well tolerated with no severe adverse effects (Noguchi et al. In this trial. Ganoderma lucidum (Reishi. serum prostate-specific antigen. or testosterone levels. lucidum inhibits proliferation of human breast cancer cells and contains biologically active compounds with specificity against the estrogen receptor and NF-kappaB (transcription factor) signalling (Jiang et al. Alteration of serum prostate-specific antigen doubling time did not correlate with that of serum testosterone levels. laboratory values. Lingzhi) has been reported to suppress the invasive behaviour of breast cancer cells by inhibiting the transcription factor NF-kappaB and to inhibit the growth of MDA-MB-231 breast cancer cells by modulating Akt/NF-kappaB signaling (Jiang et al. A double-blind. randomized.antigen was observed. residual urine. tsugae have been reported to have anti-tumour activities in human breast cancer cells and immunomodulatory activities in murine lymphocytes. In addition.. G. 88 men over the age of 49 years who had slight-to-moderate LUTS were randomly assigned to 12 weeks of treatment with G. lucidum extract (6mg once per day) or placebo. Aqueous extracts of fruiting bodies of Ganoderma lucidum. The primary outcome measures were changes in the International Prostate Symptom Score (IPSS) and variables of uroflowmetry. A subsequent study by the same group on the proliferation of human estrogen-dependent (MCF-7) and estrogen-independent (MDA-MB-231) breast cancer cells has reported that G. lucidum was effective and significantly superior to placebo for improving total IPSS with 2. and G.

. lucidum extract (GLE) on cell proliferation (anchorage-dependent growth) as well as colony formation (anchorage-independent growth) of breast cancer cells. which is involved in hormonal signalling cascades.. A protein from Ganoderma lucidum has also been shown to effectively promote the activation and maturation of immature human monocyte-derived dendritic cells. lucidum on oxidative stress-induced metastatic behaviour of poorlyinvasive MCF-7 breast cancer cells has also been studied and it has been shown that G. 186 . lucidum on cell migration was mediated by the suppression of secretion of interleukin-8 from MCF-7 cells exposed to oxidative stress. Although individual GTE and GLE independently inhibited adhesion. The effect of G. These immunomodulatory effects were shown to be mediated via NF-kappaB and Mitogen Activated Protein Kinase (MAPK) pathways. preferring a Th1 response. which resulted in the down-regulation of expression of c-fos. lucidum extracts for the suppression of growth and invasiveness of metastatic breast cancers (Thyagarajan et al. their combination demonstrated a synergistic effect. The biological effect of G. 2006). The effect was mediated by the down-regulation of expression of the oncogene c-myc in MDA-MB-231 cells. migration and invasion of MDA-MB-231 cells. lucidum suppressed oxidative stress stimulated phosphorylation of extracellular signal-regulated protein kinases (Erk1/2). These results suggest that G. which was mediated by the suppression of secretion of urokinase plasminogen activator (uPA) from breast cancer cells suggesting a potential use of combined green tea and G.ingredients (Yue et al.. G. lucidum inhibited oxidative stress-induced migration of MCF-7 cells by the downregulation of mitogen activated protein kinase (MAPK) signalling.. 2006). 2007). 2009).. An extract of Ganoderma lucidum has also been reported to reduce chemically-induced mammary adenocarcinomas in Sprague Dawley rats (Lakshmi et al. lucidum inhibited the oxidative stress-induced invasive behaviour of breast cancer cells by modulating Erk1/2 signaling and could possibly be considered as an antioxidant in adjuvant cancer therapy (Thyagarajan et al. 2009b). suggesting that the protein may possess a potential effect in regulating immune responses (Lin et al. A further study by the same group has also shown that an extract from green tea (GTE) increased the anti-cancer effect of G. and in the inhibition of transcription factors AP-1 and NF-kappaB.

lucidum did not affect their immune functions. Larger double blind trials are required to show if this is a real effect. lucidum have also been shown to strongly generate reactive oxygen species (suggesting immunomodulatory effects) in human PBMCs and K 562 cells in vitro (Wei et al. In 41 assessable cancer patients. Karst.. Ganoderma lucidum (Leyss: Fr) Karst. 2008).. 2010). including granulocyte colony-stimulating factor. Polysaccharide fractions of Ganoderma lucidum have been shown to have potent immunomodulating effects in pre-clinical trials. Subsequently.. Ganoderma lucidum also induced both nitric oxide and inducible nitric oxide synthase (iNOS). lucidum polysaccharides (Ganopoly) in patients with advanced colorectal cancer. and iNOS in a concentration-dependent manner and expression of toll-like receptor (TLR)2.. TLR4. lucidum in the form 187 .7 mouse macrophage cell secretion of several cytokines. Forty-seven patients were enrolled and treated with Ganopoly at 5.. 2009a) and WEHI-3 leukemic BALB/c mice (Chang et al.4 g/day for 12 weeks. and tumor necrosis factor-alpha.e.) P. tissue inhibitor of metalloproteinase-1. which activate NF-kappa B and prompt the secretion of cytokines (Batbayar et al. 2008). Treatment with an inhibitor of nuclear factor-kappa B (NF-kappa B) reduced the induction of IL-1. A clinical study of healthy volunteers demonstrated that G.: Fr. 2009b). has also been shown to trigger immunomodulatory effects and reduce nitric oxide synthesis in Swiss male mice (Rubel et al. High immunomodulatory and protective effects against sarcoma 180 in mice fed with Ling Zhi or Reishi mushroom Ganoderma lucidum (W.. 2011). Phenolic compounds present in mushroom extracts from G. likely by binding to dectin-1 and toll-like TLR-2/6 receptors. Curt. not double blind or placebo controlled) aimed to evaluate the effects of water-soluble G. The result indicates that Ganoderma lucidum induces macrophage secretion of inflammatory cytokines. and TLR6 was increased by Ganoderma lucidum treatment. Ganoderma lucidum binds to dectin-1 and has been shown to induce RAW264. interleukin (IL)-6. which was also potentiated by the presence of lipopolysaccharide. IL-6. It has been proposed that the immune-regulatory activity and selenium-containing attribute of proteins from Ganoderma lucidum or selenium-enriched G. Gandoderma lucidum extracts have also been shown to promote immune responses in normal BALB/c mice (Chang et al.. treatment with Ganopoly tended to increase mitogenic reactivity to phytohemagglutinin (Gao et al.Innate immune cells are activated by the binding of beta-glucan to the dectin-1 receptor. an open-labeled study (i. regulated upon activation normal T cell expressed and secreted (RANTES). (Aphyllophoromycetideae) mycelium has also been reported (Rubel et al. 2005).

The effects of Ganoderma lucidum (Basidiomycetes) polysaccharide (GL-PS) extract on tumour volume and T(CD4+/CD8+) ratio of tumour infiltrating lymphocytes (TILs) in breast cancer bearing mice have been studied. increased p53 but inhibited Akt expression (Zhao et al. 2011). An alcohol extract from the spore of Ganoderma lucidum has also been shown to inhibit the in vitro proliferation of human umbilical vein endothelial cells and MDA-MB-231 human breast cancer cells. 2006). Ganoderma lucidum also induced cell cycle arrest at the G2/M phase. a triterpenoid isolated from Ganoderma lucidum.. The mechanisms involved G1 cell cycle arrest. inhibits cell proliferation and colony formation in MCF-7 human breast cancer cells. Lucidenic acid B-induced apoptosis involved release of mitochondria cytochrome c and subsequently induced the activation of caspase-9 and caspase-3. Ganoderic acid DM (GADM).. 2004). may contribute to their antitumor activity (Du et al. 2012). Furthermore. induced apoptosis by activating caspase 3. The authors concluded that GL-PS can exhibit a potent immunomodulatory effect and may be used for potentiation of the immune system against diseases such as cancer and other conditions in which the immune response has been compromised (Mojadadi et al. intraperitoneal injection of this extract in breast cancer bearing mice could increase T-cell infiltration into the tumour.. Ganoderma lucidum has been shown to significantly decrease ovarian cancer cell numbers in vitro in a dose-dependent manner. and apoptosis induced by GADM may be partially due to GADM-induced DNA damage of the breat cancer cells (Wu et al. Further fractionation of the alcohol extract revealed that the ethyl acetate fraction inhibited both cell lines in a dose-dependent manner from 2 to 40mg/ml (Lu et al. C. Ganoderma lucidum also inhibited colony formation.. cell migration and spheroid formation. Lucidenic acids isolated from Ganoderma lucidum (YK-02) decreased cell population growth of HL-60 leukemia cells. The results indicated that GL-PS (100mg/kg/day) could effectively increase the delayed type hypersensitivity response against sRBC in BALB/c mice. Pretreatment with a general caspase-9 inhibitor (Z-LEHD-FMK) and caspase-3 inhibitor (Z-DEVD-FMK) prevented lucidenic acid B from inhibiting cell viability 188 . Treatment of HL-60 cells with lucidenic acid A. and N caused cell cycle arrest in the G1 phase.of selenocysteine and selenomethionine. which were followed by cleavage of poly(ADP-ribose) polymerase (PARP). 2010)..

. 2006). 2010d). The inhibitory effect of GLE-2 was much stronger than that of GLE-1. lucidum extracts inhibit proliferation of human colorectal cancer cells and possesses antioxidant activity (Xie et al. Aqueous extracts of Ganoderma lucidum (30. This was confirmed by spin-trapping experiments showing that SeGLPr exhibited higher activities of scavenging superoxide and hydroxyl radicals than its analog. 2004b). which increased with the increase of Se content as suggested by chemiluminescence analysis..1%) have a relatively high Antioxidant Index (% relative to quercetin) in vitro (Abdullah et al. 2012). 2010). and Ganoderma lucidum (Lingzhi) polysaccharides have been shown to have an inhibitory effect on cervical cancer cells (CA Ski and HeLa cells) (Chen et al. Ganoderma lucidum has also been shown to inhibit proliferation in a dose.in HL-60 cells (Hsu et al. All Se-GLPr samples showed stronger 189 . Protein extracts from selenium-enriched Ganoderma lucidum (Se-GLPr) have been reported to possess strong DNA protective effects from oxidative damage. 2008b). and a triterpenoid fraction without polysaccharides (GLE-2) were analyzed.. Ganoderma lucidum has also been shown to induce apoptosis in NB4 human leukemia cells and to affect the signal transduction kinases Akt and Erk (Calvino et al. Aqueous extracts of the sporophores of eight mushroom species have been assessed for their ability to prevent H2O2-induced oxidative damage to cellular DNA using the singlecell gel electrophoresis ("Comet") assay. The effects of Ganoderma lucidum on SW 480 human colorectal cancer cells have been evaluated. 2009). A fraction containing mainly polysaccharides (GLE-1).... GLE-1 inhibited DNA synthesis in the cells and reduced the formation of DPPH radicals indicating that G.. These edible mushrooms therefore represent a valuable source of biologically active compounds with potential for protecting cellular DNA from oxidative damage (Rocha et al. 2002). common Ganoderma lucidum extract. indicating indirectly that Se plays an important role in increasing the antioxidant activities of protein extracts. The data showed that both GLE1 and GLE-2 significantly inhibited the proliferation of SW 480 cells.. Further work by the same group has also shown that Ganoderma lucidum polysaccharides induce macrophage-like differentiation in human leukemia THP-1 cells via caspase and p53 a ctivation (Hsu et al.and timedependent manner and induce apoptosis in human prostate cancer cells PC-3 (Jiang et al. The highest genoprotective effects were obtained with cold (20ºC) and hot (100ºC) water extracts of Agaricus bisporus and Ganoderma lucidum fruit bodies. respectively.

immune status. A hot water extract from Ganoderma lucidum has been shown to have an antioxidative effect against heart toxicity in mice. 2009). Polysaccharide extracts from Se-enriched G. G.2-diphenyl-1-picrylhydrazil (DPPH). The results showed no evidence of liver. 2. 2004). with the results indicating that the lucidenic acids isolated from G. DNA damage. 190 . lucidum (YK-02) were anti-invasive bioactive components on human hepatoma carcinoma cells (Weng et al. as well as markers of liver and renal toxicity. No significant change in any of the biomarkers was found. Ganoderma lucidum exhibited a dose-dependent antioxidative effect on lipid peroxidation and superoxide scavenging activity in mouse heart homogenate.. cross-over intervention study on a range of biomarkers for human health. lucidum increased antioxidant status in liver mitochondria of aged mice compared with the aged controls. Furthermore. The authors concluded that this effect of Ganoderma lucidum may protect the heart from superoxide induced damage (Wong et al. 2004). 2'-azinobis (3-ethylbenzothiazolin-6-sulphonic acid) (ABTS) radical scavenging activities and ferric reducing antioxidant power (FRAP) as well as superoxide and hydroxyl radical scavenging activities.activities of attenuating the production of superoxide radical than that of hydroxyl radical (Zhao et al.. equivalent to 13.44g Lingzhi/d. The extract possessed significant 2. A more recent study has examined the effects of an extract of Ganoderma lucidum for its free-radical scavenging property and for effects on liver mitochondrial antioxidant activity in aged BALB/c mice (50 and 250 mg/kg body weight for 15 days) (Cherian et al.. 2008). and inflammation. cardiovascular disease (CHD) risk. 2007). renal or DNA toxicity with Lingzhi intake (Wachtel-Galor et al.. 2004). placebo-controlled.. this result indicated that heart damage induced by ethanol showed a higher malonic dialdehyde level compared with heart homogenate treated with Ganoderma lucidum. The study investigated the effects of 4 weeks Lingzhi supplementation (1.. lucidum have also been shown to protect DNA from hydroxyl radical oxidative damage in a dose dependent manner (Zhao et al.2g fresh mushroom/d) on a range of biomarkers for antioxidant status. The anti-invasive effect of lucidenic acids isolated from a Ganoderma lucidum strain (YK02) against human hepatoma carcinoma cells have been evaluated. A human toxicological study has evaluated the consumption of Lingzhi (Ganoderma lucidum) in a double-blinded.

Ganoderma lucidum has also been shown to inhibit cell growth and disruption of cell cycle progression via down regulation of cyclin D1 in the ovarian cancer cell line OVCAR-3. In contrast. Sarcoma 180. lucidum on the healing of gastric ulcers induced by acetic acid in the rat has subsequently been studied. The effect of the PS fraction from G. T-47D.. The polysaccharide (PS) fractions from several medicinal herbs have been reported to have anti-ulcer effects against experimental ulcers in the rat. The results indicated that oral administration of G. Chemopreventive activities were demonstrated by suppression of oxidative stress via the induction of antioxidant SOD and catalase as well as the phase II detoxification enzyme NAD(P)H:quinone oxidoreductase 1 (NQO1) and glutathione S-transferase PI (GSTP1) via the Nrf2 mediated signaling pathway known to provide chemoprotection against carcinogenicity (Hsieh and Wu. The water-soluble PS fractions from Ganoderma lucidum (Reishi mushroom) have been shown to inhibit indomethacin-induced gastric mucosal lesions in rats. lucialdehydes A .. 2010b).Triterpene-enriched extracts from Ganoderma lucidum have been shown to inhibit growth of human hepatoma Huh-7 cells via suppression of protein kinase C.C. lucidum PS at 0. respectively. additional rats were treated with 10M 191 . the extracts did not inhibit growth of Chang liver cells.0g/kg for 2 weeks caused a significant acceleration of ulcer healing by 40. more recent data have proposed that the mechanisms involved (at least in human gastric carcinoma cells) involve caspase pathways which are associated with inactivation of the Akt signalling pathway (Jang et al.. and Meth-A tumour cell lines) (Gao et al. from the fruiting bodies of Ganoderma lucidum. Three triterpene aldehydes. however. 2010). The induction of apoptosis by extracts of Ganoderma lucidum have previously been reported. a normal human liver cell line (Lin et al. In mechanistic studies. 2010d). Polysaccharides from the Lingzhi (Ganoderma Lucidum) have been shown to decrease CyclinB1 mRNA expression in cervical cancer CaSki cells and inhibit CaSki and HeLa cell proliferation (Chen et al. 2002). have been shown to have cytotoxicity against murine and human tumour cells (Lewis lung carcinoma (LLC)..5 and 1. activating mitogenactivated protein kinases (intermediates in hormonal signalling pathways) and G2-phase cell cycle arrest. 2003).9%. Induction of apoptosis and alterations in signal transduction kinases (Akt and Erk) by active fractions from Ganoderma lucidum have also been reported in human leukemia cells (Calvino et al.1% and 55. 2011)..

Cholesterol-lowering properties of Ganoderma lucidum have been demonstrated in vitro. 2002b). 2007). The administration of the EXBP (100mg/kg body weight) substantially reduced the plasma total cholesterol. Organic fractions containing oxygenated lanosterol derivatives inhibited cholesterol synthesis in T9A4 hepatocytes. and in hamsters and mini-pigs. triglyceride. phospholipid levels. and phospholipid levels by 22.and HDL cholesterol 20. 2011). respectively. The hypolipidemic effect of the exo-biopolymer (EXBP) and endo-biopolymer (ENBP) produced from a submerged mycelial culture of Ganoderma lucidum has been investigated in dietary-induced hyperlipidemic rats.5%. In minipigs. and 53. 7. 2004). low-density lipoprotein (LDL) cholesterol.. and decreased cholate (Berger et al. 28. and atherogenic index by 31. 39. 10. Pleurotus florida and Pleurotus pulmonaris. Hypolipidemic effects were achieved in both the EXBP.. LDL. A hypolipidemic effect of Ganoderma lucidum (Leyss:Fr) Karst has also been demonstrated in a mouse model (Rubel et al. or 14 days. and 12. lucidum PS is an active component with healing efficacy on acetic acid-induced ulcers in the rat.2%. respectively. and 18%. respectively. increased faecal cholestanol and coprostanol. Treatment with G. Ganoderma lucidum (2.. The results indicated that G. lucidum PS at 1. lucidum PS (1. Furthermore.and ENBP-treated groups.1%.. and high density lipoprotein (HDL) by11. the high-density lipoprotein (HDL) cholesterol and ratio of HDL cholesterol to total cholesterol were significantly increased (Yang et al. 23.0%.1%.8%. Ganoderma lucidum. 2.4%.0%. have been reported to have significant antioxidant activities (Ajith and Janardhanan. however. The EXBP also lowered the liver total cholesterol. when compared to the control group. 2004). 192 . the former proved to be more potent than the latter. 5% Ganoderma lucidum did not affect low density lipoprotein (LDL) but decreased total cholesterol (TC) by 9.5% Ganoderma lucidum decreased TC. 35. 27. triglyceride.0g/kg) for 3.4%. and then treated with G. ex vivo.acetic acid to induce acute ulcers. as well as Phellinus rimosus.9%.5 and 5%) had effects on several faecal neutral sterols and bile acids. which may represent a useful preparation for the prevention and treatment of peptic ulcers (Gao et al. In hamsters.0 g/kg significantly suppressed or restored the decreased gastric mucus levels and increased gastric prostaglandin concentrations compared with the control group.

The data provide evidence that GL-M has immunomodulating effects on human immune cells and may be of use as a natural adjuvant for cancer immunotherapy with dendritic cells (Chan et al. Ganoderma lucidum mycelia did not potentiate nitric oxide production in RAW264. In contrast to GL-S. GL-M induced the proliferation of PBMCs and monocytes. 2006).6mg/ml) have also been reported to stimulate tumour necrosis factor-alpha (TNF-alpha) and IL (interleukin)-6 production after 8h of treatment in human whole blood.7 cells. 2009). Interestingly. Ling Zhi extract (LZE) is a herbal mushroom preparation that has been shown to induce apoptosis anti- 193 . and CD86. An electrophoretic mobility shift assay revealed that the Ganoderma lucidum mycelia (1. 2005). IFN (interferon)-gamma release from human whole blood was also enhanced after 3 days of culture with Ganoderma lucidum mycelia (0. Ganoderma lucidum mycelia (0... Both extracts stimulated Th1 and Th2 cytokine mRNA expression.2-1. The effects on the phenotypic and functional maturation of human monocyte-derived DCs were also investigated. However.0mg/ml). An extract from Ganoderma lucidum has been reported to have apoptotic and antiinflammatory functions in HT-29 human colonic carcinoma cells. CD80. Dendritic cells (DCs) are antigen-presenting cells and their role in DC-based tumour vaccines has been well defined.7 cells. 2006).. GL-M-treated DCs only modestly enhanced lymphocyte proliferation in allogenic mixed lymphocyte culture with mild enhancement in Th development. whereas GL-S showed a mild suppressive effect. A polysaccharide purified from Ganoderma lucidum has also been shown to induce gene expression changes in human dendritic cells and promotes T helper 1 immune response in BALB/c mice (Lin et al. Ganoderma lucidum has also been shown to enhance the expression of CD40 and CD80 molecules on human peripheral blood monocytic cells derived from both sexes in a dose-dependent manner (Ahmadi and Riazipour. and also reduced fluorescein isothiocyanate-dextran endocytosis.6mg/ml) activated kappaB DNA binding activity in RAW264.2-1. but GL-M was a relatively stronger Th1 stimulator. These results provide supporting evidence for the immunomodulatory effect of Ganoderma lucidum mycelia (Kuo et al.Possible immuno-modulating effects of Ganoderma lucidum mycelium extract (GL-M) and spore extracts on human immune cells have been studied. GL-M enhanced maturation of DCs in terms of up-regulation of CD40. The differential effect of GL-M and GL spore extract (GL-S) on proliferation and Th1/Th2 cytokine mRNA expression of human peripheral blood mononuclear cells (PBMCs) and monocytes has been evaluated.

p21 and cyclin E were not affected. which is involved in the progression of colorectal cancer.000mg/ml decreased the expression of cyclooxygenase-2 mRNA. macrophage inflammatory protein 1-delta. Increasing concentrations reduced prostaglandin E2 production.. 2010c). A marked inhibitory effect was also seen on Cdk-4 and PCNA expression. vascular epithelial growth factor. 2004). In HT29 human colon cancer cells. and suppressed tumor growth in a xenograft model of human colon adenocarcinoma cells HT-29 implanted in nude mice without any side-effects and inhibited expression of cyclin D1 in tumors (Jedinak et al. but increased nitric oxide production. a human colon carcinoma cell line. RT-PCR showed that LZE at a concentration of 5. which leads to downregulated expression of matrix metalloproteinase-9 (MMP-9). Ganodermanontriol also caused a dose-dependent increase in protein expression of Ecadherin and beta-catenin in HT-29 cells. as well as inhibitory effects on cytokine expression during early inflammation in colonic carcinoma cells (Hong et al. Animal and Lewis Ganodermanontriol. HT-29. Ganoderic acid T (GA-T) of Ganoderma lucidum inhibited proliferation of HCT-116 cells. a lanostanoid triterpene from Ganoderma lucidum has been shown to be able to modulate of the beta-catenin pathway. in a dose. Ganoderma lucidum inhibited proliferation of HCT-116 and HT-29 colon cancer cells without a significant effect on cell viability.000 mg/ml.000mg/ml to HT-29 cells reduced the expression of interleukin-8. Cell aggregation and adhesion assays showed that GAT promoted homotypic aggregation and simultaneously inhibited the adhesion of HCT-116 cells to the extracellular matrix (ECM) in a dose-dependent manner (Chen et al. Wound healing assays indicated that GA-T also inhibited the migration of HCT-116 cells in a dose-dependent manner. Among 42 cytokines tested by protein array in this study. supplementation of LZE at doses of 500 and 5. a highly metastatic human lung tumor cell line.. and urokinase-type plasminogen activator (uPA). and platelet-derived growth factor. GA-T inhibited the nuclear translocation of nuclear factor-kappa B (NF-kappa B) and the degradation of inhibitor of kappa B-alpha (I kappa B alpha). 2011b). inducible nitric oxide synthase (iNOS). triterpenes from Ganoderma lucidum have also been shown 194 . and suppressed the migration of 95-D cells.. The extract caused no cytotoxicity in HT-29 cells at doses less than 10. In addition. LZE treatment induced apoptosis by increasing the activity of caspase-3. while ganodermanontriol inhibited transcriptional activity of beta-catenin and protein expression of its target gene cyclin D1 in a dose-dependent manner. whereas expression of Cdk-2.inflammatory action and differential cytokine expression during induced inflammation in the human colonic carcinoma cell line. These results suggest that LZE has pro-apoptotic and anti-inflammatory functions.and time-dependent manner.

It was also found that the water-soluble polysaccharide isolated from the fruit body of Ganoderma lucidum was as effective as a hot-water extract in protecting against hydroxyl radical-induced DNA strand breaks. indicating preferential protection to normal tissues and possible use as an adjuvant in radiotherapy. The mitochondrial respiratory chain is a direct intracellular source of reactive oxygen species. The level of lipid peroxidation was significantly lowered in the Ganoderma lucidum treated group compared to the aged controls. as well as protection against DNA damage induced by metal-catalyzed Fenton reactions and UV irradiation.. although the evidence was based on in vitro tests using isolated DNA. 2010).to induce programmed cell death (Type II-autophagy) via a mechanism involving inhibition of p38 mitogen-activated kinase (p38 MAPK) (Thyagarajan et al. then further studies would be warranted to evaluate possible future applications against ageing associated neurodegenerative diseases. The activity exhibited by the extract of Ganoderma lucidum was partially correlated to its antioxidant activity. The potential of an Ganoderma lucidum extract as a radioprotector and antioxidant defense against oxygen radical-mediated damage has been studied and it was demonstrated that a hot-water extract of Ganoderma lucidum had good radioprotective ability. 2010). 195 . Reactive oxygen species have been reported to be involved in the pathogenesis of a number of age-associated human health conditions.. for tumour regression and prevention of radiationinduced cellular damage in normal tissues (Gopakumar et al.. revealed that there was significant reduction in radiation-induced damage to cellular DNA in normal tissues compared to the tumour. 2010). Polysaccharides isolated from Ganoderma lucidum have also been reported to enhance the repair of radiation induced DNA strand breaks in human cells after 120min of exposure (Pillai et al. 2009). Oral administration of Ganoderma lucidum extract (GLE) to tumor-bearing Swiss albino mice along with exposure to gamma radiation has been shown to result in tumour regression. Ganoderma lucidum (50 and 250 mg/kg) has been shown to enhance the activities of mitochondrial dehydrogenases and complex I and II of the electron transport chain in the brain of aged male Wistar rats (Ajith et al. If Ganoderma lucidum is able to improve the function of mitochondria in the aged rat brain. Single-cell gel electrophoresis (comet assay) on cells of normal and tumour tissues from tumour-bearing animals treated with GLE and radiation. 1999).. indicating that the polysaccharide compound is associated with the protective properties (Kim and Kim.

. 2009)..An aqueous extract of Ganoderma lucidum (0. IL-1 beta. lucidum-treated Ovx rats showed improved bone density compared with the Ovx rats. 2009).03 and 0. Exposure of bone marrow macrophages to GLIS resulted in significant increases in NO production. lucidum).. 2007). IL-12p35. 2009). while Ganoderma lucidum polysaccharides have also been shown to significantly and dose-dependently increase nonenzymic and enzymic antioxidants. and TNF-alpha gene expression and levels of TNF-alpha..3g/kg) has been shown to lower the serum glucose level in obese/diabetic (+db/+db) mice after one week of treatment whereas a reduction was observed in lean (+db/+m) mice only fed with 0. induction of cellular respiratory burst activity. 2011). serum insulin level and reduce lipid peroxidation and blood glucose levels in streptozotocin-induced diabetic rats (Jia et al. Ganoderma lucidum has been reported to possess both hypoglycaemic and antihyperglycaemic effects in Wistar rats (Mohammed et al. 2011. possibly providing an anti-inflammatory effect in a mouse model of colitis has been reported (Hanaoka et al. A higher hepatic PEPCK gene expression was found in +db/+db mice. 2011).. indicating that GLIS activates the immune system by modulating cytokine production (Ji et al. These data demonstrate that G. lucidum (0.3g/kg) markedly reduced PEPCK gene expression in +db/+db mice whereas the expression of PEPCK was attenuated in +db/+m mice (0... IL-12p40. Enhaced proliferation of bone marrow macrophages in a dose-dependent manner by Lingzhi or Reishi medicinal mushroom Ganoderma lucidum immunomodulating substance (GLIS) has been demonstated. and IL-12 secretion. lucidum consumption can provide beneficial effects in treating type 2 diabetes mellitus (T2DM) in mice by lowering the serum glucose levels through the suppression of hepatic PEPCK gene expression (Seto et al. Zhe et al. IL-18. IL-6. and increased levels of IL-1 beta. Ethanol extracts of Ganoderma lucidum have been evaluated against the ovariectomized (Ovx)-induced deterioration of bone density in 11-week-old female Sprague Dawley (SD) rats (Miyamoto et al. G. lucidum at the fourth week.3g/kg of G.3g/kg G. The induction of granulocyte macrophage colony-stimulating factor (GM-CSF) production by water-soluble. polysaccharide components of Ganoderma lucidum (Reishi) mycelia. The results showed that the G. 196 .03 and 0.

proliferation.. with E.Crude dichloromethane. whereas it increases the expression of IL8 (Martinez-Montemayor et al. an immunomodulatory protein cloned from Ganoderma lucidum (Reishi or Ling Zhi) inhibits the proliferation of A549 human lung cancer cells.) P. The mycelial culture of Ganoderma lucidum has been shown to be highly active against human pathogenic bacteria Escherichia coli. lucidum and their effects have also 197 . and alkaloids. The extract of G.. Reishi decreased the expression of genes involved in cancer cell survival. 2012). terpenoids. 2011). water. invasion and metastasis. The evidence for the anti-cancer effects of Ganoderma lucidum has been reviewed (Yuen and Gohel. Recombinant Lz-8 (rLz-8) also induced endoplasmic reticulum stress-mediated autophagic cell death in the human gastric cancer cell line SGC-7901.. but caspase inhibitors did not prevent rLz-8-induced cell death. while the active compounds in G. at oral doses of 500 mg/kg and 1000 mg/kg has been shown to attenuate Indomethacin-induced gastric ulceration in rats (Rony et al.. The antitumor effect was via a modulation of p53 via ribosomal stress. although it is unknown which compounds in the extract were responsible for the anti-viral effects (Lai et al.. with the dichloromethane extract being the most active. and polysaccharide extracts of Ganoderma lucidum all suppressed HPV 16 E6. 2011a). 2010c).coli having the highest susceptibility to the mushroom mycelia (Ofodile et al. 2011). in mice transplanted with Lewis lung carcinoma cells (Wu et al.. ethanol. Staphylococcus aureus. lucidum contained flavonoids. These results indicate that GA-T effectively inhibits cancer cell invasion in vitro and metastasis in vivo (Chen et al. Klebsiella pneumoniae and Pseudomonas aeruginosa. Karst. An ethanol extract of Ganoderma lucidum (Fr. 2011). rLZ-8 inhibited lung cancer cell growth in vitro and also in vivo. Ganoderma lucidum (Reishi) selectively inhibits cancer cell viability in inflammatory breast cancer although it does not affect the viability of noncancerous mammary epithelial cells. Recombinant Ling Zhi-8 (rLZ-8). 2010).. and therefore the autophagic response induced by rLz-8 is independent of caspase activation (Liang et al. Reishi has been shown to inhibit cell invasion and disrupt the cell spheroids that are characteristic of inflammatory breast cancer. Lung Carcinoma (LLC) model experiments have demonstrated that GA-T suppressed tumor growth and LLC metastasis and down-regulates MMP-2 and MMP-9 mRNA expression in vivo. 2005). phenolics.

the pharmacological aspects. 2010b). phosphatidylinositol 3-kinase (PI 3-kinase) or Akt kinase (protein kinase B) (Weng and Yen. 2009). Grifola Frondosa (Maitake) An open trial with 80 patients with polycystic ovary syndrome at three clinics in Japan has been undertaken. The data suggest that the Maitake extract described in this study may induce ovulation in patients with polycystic ovary syndrome and may be useful as an adjunct therapy for patients who failed first-line treatment with clomiphene citrate (Chen et al. A Systematic Review (the ‘gold standard’ of reviews) has evaluated the scientific evidence on Grifola frondosa (Maitake).0006). respectively by the patients (NS). and dosing 198 . toxicology.9% (20/26) and 93. More recently. cultivation methods and bioactive metabolites from Ganoderma lucidum and their potential role in various therapeutic applications have been reviewed (Sanodiya et al. adverse effects. kinetics/dynamics. In the combination therapy. Eighteen (18) patients who did not respond to MSX or CC were subjected to combination therapy of MSX and CC for up to 16 weeks. The ovulation rates for MSX and CC were: 76. respectively. 7 of 7 patients who failed in MSX monotherapy and 6 of 8 patients who failed in CC monotherapy showed ovulation. A further review on the potential therapeutic properties of Ganoderma lucidum has also recently been published (Deepalakshmi and Mirunalini. interactions..been reviewed (Boh et al. Seventy-two patients were randomly assigned to receive Maitake extract (SX-fraction: MSX) or clomiphene citrate (CC) monotherapy for up to 12 weeks. history. lucidum on cancer invasion and metastasis have been reviewed. Furthermore. 2010).. and 41. 2007). Twenty-six (26) patients in the MSX group and 31 in the CC group were evaluated for ovulation.9% (58/83). the in vitro and in vivo effects of G. by the cycles ( p=0. 2011).7% (30/72) and 69. Eight (8) patients with documented history of failure to CC received combination therapy from the beginning. with the authors concluding that these effects occur through modulation of the phosphorylation of extracellular signal-regulated kinase (ERK1/2).. folkloric precedent. pharmacology.5% (29/31). including expert opinion.

A further study by the same group has recently reported the purification of an anti-viral protein from an extract of Grifola frondosa (Maitake) fruiting bodies. might provide a potentially effective therapy against chronic hepatitis B virus infections (Gu et al. adverse effects. 2006).2. Higher concentrations (125 and 500 µg/ml) also significantly reduced the severity of HSV-1 induced blepharitis. The results showed that GF-D or IFN alone could inhibit HBV DNA in the cells with the 50% inhibitory concentration (IC50) of 0.15 cells). 2009). Maitake D-fraction is a polysaccharide extracted from the Maitake mushroom (Grifola frondosa S. indicating that the protein is likely to be a novel anti-viral protein (Gu et al.15 cells. The literature collected pertained to efficacy in humans. and mechanisms of action. While animal studies report hypoglycaemic effects and anti-cancer and immunostimulatory effects.. respectively. Using normal C3H/Hej mice.F. This 9-fold increase in anti-viral activity of IFN suggested that GF-D could synergize with IFN. It was reported that the protein directly inactivated HSV-1 while simultaneously inhibiting HSV-1 penetration into Vero cells. The N (amino)-terminal sequence of the protein consisted of an 11 amino acid peptide. In combination with 0.59mg/ml and 1399 IU/ml. the apparent IC50 value for IFN was 154 IU/ml. Gray). The protein inhibited herpes simplex virus type 1 (HSV-1) replication in vitro with an IC50 value of 4.2.2.15 cells (2. Topical administration of the protein to the mouse cornea resulted in a significant decrease in virus production. alteration of laboratory assays.45mg/ml GF-D. NH2-REQDNAPCGLN-COOH that did not match any known amino acid sequences. dosing. HBV DNA and viral antigens were analyzed by a quantitative real-time polymerase chain reaction and end-point titration in radioimmunoassays. in combination with human interferon alpha-2b..3. The results indicate that the Grifola frondosa extract. The combination of GF-D and IFN for anti-HBV activity was also evaluated and it was found that they synergistically inhibited HBV replication in 2. use in pregnancy and lactation. neovascularization. precautions. and stromal keratitis in a murine model. its effects on the natural immune 199 . 2007). the authors concluded that there was a lack of systematic study on the safety and effectiveness of Maitake in humans and future randomized controlled trials are required before efficacy in humans can be substantiated. interactions. GF-D) and its combination with human interferon alpha-2b (IFN) has been investigated for an inhibitory effect on hepatitis B virus (HBV) in HepG2 2.. respectively.1µg/ml and a therapeutic index >29. A fraction extracted from Grifola frondosa (Maitake.(Ulbricht et al.

and hence administration of D-fraction to healthy individuals may serve to prevent infection (Kodama et al. Anti-tumour activity induced by an extract from Grifola frondosa in a macrophage cell line. by normal mice.7 has been reported to be mediated via a nitric oxide-mediated pathway (Sanzen et al. have been investigated.system. including macrophages.human committed hematopoietic progenitor (HPC) cells compared to the conventional stem cell culture medium.. Beta glucan from Grifola frondosa (Maitake) has recently been shown to enhance umbilical cord blood stem cell transplantation (from full-term infants) in the nonobese diabetic/severe combined immunodeficient (NOD/SCID) mouse.. The Maitake beta glucan (MBG) enhanced mouse bone marrow (BMC) and human umbilical cord blood (CB) cell granulocyte-monocyte colony forming unit (GM-CFU) activity in vitro and protected GMCFU forming stem cells from doxorubicin (DOX) toxicity. The results indicated that the D-fraction stimulated the natural immunity related to the activation of NK cells indirectly through IL-12 produced by macrophages and dendritic cells. A study has also suggested that oral administration of a submerged cultivated G. 2009a). 2008).. 2001). More CD34+ human cord blood cells were also retrieved from mouse spleen in beta glucan treated mice at 6 days after transplantation. A subsequent study from this group has suggested that the mechanism by which NK cells are activated is mediated through cytokines produced by antigenpresenting cells (Kodama et al. RAW264. that can modulate natural and specific immune responses. Similarly. D-Fraction was administered to the mice intraperitoneally for 3 consecutive days. NK cells attack cells infected with pathogens such as bacteria and viruses and produce cytokines. 2003). dendritic cells. and natural killer (NK) cells. 2010).. frondosa mixture. Oral administration of MBG to recipient NOS/SCID mice led to enhanced homing at 3 days and engraftment at 6 days in mouse bone marrow compared to control mice. may enhance host innate immunity against foreign pathogens without eliciting an adverse inflammatory response (Wang et al. The studies suggest that Maitake beta glucan promoted hematopoiesis through effects on CD34+ progenitor cell expansion ex vivo and when given to the transplant recipient could enhance CD34+ precursor cell homing and support engraftment (Lin et al. an aqueous extract from Grifola frondosa has been reported to have immuno-modulating properties via a mechanism involving the regulation 200 .. Spleen cells containing macrophages and dendritic cells were then cultured and the culture supernatants were analyzed for IL-12. such as interferon-gamma (IFN-γ). MBG promoted a greater expansion of CD34+CD33+CD38.

This effect may be due to triggering doublestranded DNA-dependent protein kinase activation that may act on the cell cycle to cease cancer cell growth. 2010). The combination of interferon-alpha2b (10000 IU/mL) and Maitake mushroom D fraction (200 g/mL) reduced growth by ~75% in T24 bladder cancer cells. but the content decreased markedly at higher temperature (20ºC) (Mizuno. while Western blot analyses of TMK-1 cells after treatment with the extract revealed increases in intracytoplasmic cytochrome c and cleavage of caspase-3 and poly(ADP-ribose) polymerase. but no expression of p21 or Bax. while not affecting the proliferation of colon26 cells in vitro. A water-soluble extract of Grifola frondosa has been shown to inhibit the proliferation of four human gastric cancer cell lines (TMK-1. The inhibition was most pronounced in TMK-1 cells. The data suggest that this extract from Grifola frondosa produces potential antitumour effects on gastric cancer via an induction of apoptosis of TMK-1 cells by caspase-3-dependent and -independent pathways (Shomori et al.of nitric oxide (NO) production both in vivo and in vitro (Cao et al. The treatment of UVA-irradiated HDF with EPS resulted in a dose-dependent decrease in the expression level of MMP-1 mRNA. via activation of cell-mediated immunity (Masuda et al... The changes in the content of anti-tumour polysaccharides from Grifola frondosa during storage have been investigated. which exhibited up to 90% inhibition after treatment with 10% extract for 3 days. 2000). The data suggested that EPS obtained 201 . MKN28. 2006)... The caspase-3 protease activities in lysates of TMK-1 cells treated with 1% or 10% of the extract were approximately 3-fold higher than in control cells. was shown to significantly inhibit tumour growth in BALB/cA mice inoculated with colon-26 cancer cells. A 23 kDa polysaccharide isolated from Grifola frondosa. MKN45 and MKN74) in a timedependent manner. 2009). the content of the anti-tumour polysaccharides showed hardly any changes. Induction of apoptosis was confirmed by fluorescence-activated cell sorting analyses. The photo-protective potential of exopolysaccharides (EPS) from Grifola frondosa HB0071 has been tested in human dermal fibroblasts (HDF) exposed to ultraviolet-A (UVA) light. It was reported that EPS had an inhibitory effect on human interstitial collagenase (matrix metalloproteinase. When the mushrooms were stored at low temperature. MMP-1) expression in UVA-irradiated HDF without any significant cytotoxicity. The synergistic potentiation of interferon activity with Maitake mushroom on bladder cancer cells has recently been reported (Louie et al. 2009).

The anti-diabetic effect of an alpha-glucan (MT-alpha-glucan) from the fruit body of Maitake mushrooms (Grifola frondosa) on KK-Ay mice (a type 2 diabetes animal model) has been evaluated. The data suggested that MT-alpha-glucan has an anti-diabetic effect on KK-Ay mice. Treatment with MT-alpha-glucan significantly increased the content of hepatic glycogen. interleukin (IL)-12 p70. on prostatic cancer cells in vitro. 2000). resulting in enhanced cellular immunity. 2005). The biological function of GFPPS1b. presumably through oxidative stress. which 202 . has been shown to suppress SGC-7901 cell growth and reduce cell survival via arresting the cell cycle in the G(2)/M phase and inducing apoptosis of tumour cells (Cui et al. 2002). leading to apoptosis. cholesterol. These results suggest that this fraction establishes Th-1 dominance which induces cellular immunity in the population that was Th-2 dominant due to carcinoma (Inoue et al.from a mycelial culture of Grifola frondosa HB0071 may contribute to an inhibitory action in photo-ageing skin by reducing the MMP 1-related matrix degradation system (Bae et al. and IL-18 by whole spleen cells and lymph node cells. The data showed that a bioactive beta-glucan from the Maitake mushroom has a cytotoxic effect. serum insulin.. but suppressed that of IL-4. free fatty acid and malondialdehyde content in liver. Maitake beta-glucan has also been shown to induce hematopoietic stem cell proliferation (Lin et al. 2007). on human prostatic cancer PC-3 cells in vitro has been evaluated. It also induced the production of interferon (IFN)gamma. the insulin binding capacity to liver crude plasma membranes increased and histopathological changes in the pancreas were ameliorated in the treatment group. 2007). The fraction decreased the activation of B cells and potentiated the activation of helper T cells. A beta-glucan extracted from the fruiting body of Grifola frondosa has been reported to activate cellular immunity and expresses anti-tumour effects. glycosylated serum protein. triglycerides. a polysaccharide-peptide isolated from cultured mycelia of Grifola frondosa GF9801. level of fasting plasma glucose. with the anti-tumour effects relating to its control of the balance between T lymphocyte subsets Th-1 and Th-2. reduced glutathione and the activity of liver superoxide dismutase and glutathione peroxidase. The potential anti-tumour effect of beta-glucan.. This mushroom polysaccharide may therefore have potential as a therapeutic modality for prostate cancer (Fullerton et al... a polysaccharide of the Maitake mushroom.. Treatment with MT-alpha-glucan significantly decreased body weight. Furthermore.

2007).30. 2001). incubated with GFfor 21 days. showed a nearly two-fold higher mineralization than cells cultured with a positive control.. 2007).. to have the ability to alter lipid metabolism by inhibiting both the accumulation of liver lipids and the elevation of serum lipids. triglyceride and phospholipids in the serum of rats in the Maitake-feed group were suppressed by 0. The cultivation of human osteosarcoma cells HOS58 for 5 days in the presence of an aqueous extract of G.8 times those in animals fed the basic feed. The effect of Grifola frondosa total water extract on two osteoblastic cell cultures (HOS58 and SaOS-2) has been investigated to determine if this mushroom has osteo-inductive properties. Enhanced insulin-hypoglycaemic activity (improvement in insulin sensitivity) has also been reported in spontaneously hypertensive rats consuming a glycoprotein extracted from Maitake mushrooms (Preuss et al. Measurement of the amount of total cholesterol and bile acid in faeces showed the ratio of cholesterol-excretion had increased 1. Maitake mushroom consumption has also been shown. The activity of alkaline phosphate and mineralization were used as indicators for the vitality and maturation of bone cells.6-0. Further studies are needed to determine the mechanism of activity of Maitake mushrooms and to establish whether their action in humans is similar to that observed in the rat model (Kubo and Nanba. indicating that Maitake inhibited lipid accumulation in the body. demonstrating the activity of Grifola frondosa extract as a bone-inducing agent (Saif et al. Plasma cholesterol concentration in rats has been shown to be reduced by feeding of mushroom Maitake (Grifola frondosa) fiber. using the same rat model system. frondosa resulted in a significant elevation of alkaline phosphatase activity of the cells in comparison to untreated cells. in Sprague-Dawley rats. A further study by the same group... Weights of liver and epididymal fat-pads were significantly lower (0.8 fold and bile acid- 203 .7 times) than those in the basic feed group. SaOS-2 cells. 1996). 2007). has also shown that consumption of dried Maitake powder (mixed with a basic high-cholesterol rat chow) cholesterol. The results demonstrated that mushroom fiber lowered the serum total cholesterol level by enhancement of the hepatic low density lipoprotein (LDL) receptor mRNA (Fukushima et al.may be related to its effect on insulin receptors by increasing insulin sensitivity and ameliorating insulin resistance of peripheral target tissues (Lei et al. Liver lipids were also measured and the values were found to be decreased by Maitake administration.

2010) with the activation of apoptosis possibly being mediated via BAK-1 gene activation (Soares et al.. Blood pressure of spontaneously hypertensive rats (SHR) has been shown to be significantly reduced by Maitake feeding for 8 weeks. at dosage levels of 500 and 2. 37. oleic. Hexane extracts of the cultured mycelia of Grifola frondosa have been shown to contain ergosterol (1). respectively. and 4%.8(14). and 1-oleoyl-2-linoleoyl-3palmitoylglycerol (3) and a fatty acid fraction containing palmitic. 1989)..22-tetraen-3-one (2). Similarly. respectively (Zhang et al.6.excretion 3 fold by Maitake treatment suggesting that Maitake consumption may help to improve the lipid metabolism as it inhibits both liver lipid and serum lipids which were increased by the ingestion of high-fat feed (Kubo and Nanba. No abnormal signs were noted in either sex of any group. 2011). beginning at a time when the animals were 10 weeks of age with well-established high blood pressure. respectively. and 42%. 70. COX-2 enzyme activity was reduced by the fatty acid fraction and compounds 13 at 250mg/mL by 99. 37. and 67%. 2002). An aqueous extract of Maitake (Grifola frondosa) mushrooms significantly reduced cellular proliferation in MCF-7 human breast cancer cells by up to 33%. There was no difference in the plasma total and free cholesterol. ergostra-4. 2003). The control group was treated with water by injection. A single oral dose of an extract of powdered Grifola frondosa. 55. and its toxicity was examined. and linoleic acids.000mg/kg has been given to 5 Crj:CD(SD) IGS strain of rats of each sex for 1 day.. Maitake also significantly induced apoptosis and cytotoxicity in these human breast cancer cells (Martin and Brophy. triglyceride and phospholipid levels between the Maitake fed animals and the control (Kabir and Kimura. When the enriched metal mycelia were subjected to a 204 . The inhibition of COX-1 enzyme by the fatty acid fraction and compounds 1-3 at 250mg/mL were 98. The inhibition of liposome peroxidation by the fatty acid fraction and compounds 1 and 2 at 100 mg/mL was 79. 48. respectively. The fatty acid fraction and compounds 1-3 showed cyclooxygenase (COX) enzyme inhibitory and antioxidant activities. 1997). No effects of powdered Grifola Frondosa were reported in either sex by body weight measurement or necropsy finding (Koike et al. Mycelia from Grifola frondosa grown in the presence of non-mycotoxic concentrations of 100 and 200 ppm of Cu or 25 and 50 ppm of Zn accumulated 200-322 ppm and 267-510 ppm of Cu or Zn.

ascorbic acid and alpha-tocopherol were found to be the major antioxidant components in the various mushroom extracts examined.. The EC50 values (<20 mg/ml) indicate that the G. The study showed that oral MBG promoted maturation of HPC to become functionally active myeloid cells and enhanced peripheral blood leukocyte recovery after chemotoxic bone marrow injury (Lin et al. frondosa extracts studied have potent antioxidative activity (Jan-Ying et al. 2010).6)-glucan obtained from Grifola frondosa induced cell proliferation and cytokine production without excessive inflammation in macrophages. Dedritic cells pulsed with colon-26 tumor lysate in the presence of the mushroom polysacchardide induced both therapeutic and preventative effects on colon-26 tumor development in BALB/c mice (Masuda et al. A polysaccharide extracted from Grifola frondosa has been shown to induce cell-mediated immunity by inducing bone marrow dendritic cell maturation and an antigen-specific Th1 response by enhancing dendritic cell-produced IL-12. in 1 g of mycelium. the solubility in the digestive fluids was 642669 ppm and 102-530 ppm.3) (1. Agaricoglycerides of the fermented mushroom Grifola frondosa at the dose level of 500 mg/kg has been shown to possess anti-inflammatory and antinociceptive effects in preclinical animal models of inflammation and in some models of pain (Han and Cui. While granulocyte colony stimulating factor (G-CSF) treatment following chemotherapy is effective in treating against bone marrow myelotoxicity. supporting its immunotherapeutic potential (Masuda et al. with the authors discussing potential uses of the mineral-enriched mycelia in capsules (in the case of Cu-enriched mycelia) and in food preparations (Figlas et al. 2011). 2010)..7-3. Antioxidant properties and antioxidant compounds of various extracts from dried Grifola frondosa (Maitake) have been determined.simulated gastrointestinal digestion in vitro. A further study from the same group has demonstrated that a soluble beta-(1. Antioxidant activity was measured using reducing power. flavonoids.5% of the recommended daily intake (RDI) for Cu and Zn. 2012)... 205 . 2010b). respectively. which represent approximately 32-33% and 0. 2011).. DPPH and superoxide radical scavenging and ferrous ion chelation activity assays. a beta-glucan extract from the Maitake mushroom Grifola frondosa (MBG) has been shown to enhance colony forming unit-granulocyte monocyte (CFU-GM) activity of mouse bone marrow and human hematopoietic progenitor cells (HPC). and to stimulated G-CSF production. Phenols.

The active compounds in Grifola frondosa (Maitake) and their effects have been reviewed (Boh and Berovic. and the least stimulation was observed with an oven-dried fruit body extract. Each of the CES-D and the ICI score after the H. Maximum stimulation of neurite outgrowth was recorded with mycelial extracts. larger studies with greater statistical power are required to confirm such outcomes. involve the renin-angiotensin system (Preuss et al. using the Kupperman Menopausal Index (KMI). Aqueous extracts of H. The effects of Hericium erinaceus on amyloid beta (25-35) peptide-induced learning and memory deficits in mice have evaluated. Anti-dementia compounds have recently been reported from the mushroom Hericium erinaceum (Kawagishi.. erinaceus therefore contain neuroactive compounds that stimulate neurite outgrowth in vitro suggesting some value in the treatment of neurodegenerative disease (Wong et al. the Pittsburgh Sleep Quality Index (PSQ1). Lion’s Mane) A human study of 30 females has investigated the clinical outcomes of 4 weeks of intake of Hericium erinaceus cookies versus placebo cookies on menopause. Hericium erinaceum extracts have also been reported to induce neurite outgrowth from neural (NG108-15) cells. 2007. 2008). sleep quality and indefinite complaints. 2010). erinaceus intake. "irritating" and "anxious" tended to be lower than the placebo group (Nagano et al. at least in part.. Shimizu et al.. 2010).. Mice were administered 10 g of amyloid beta (25-35) peptide intracerebroventricularly on days 7 and 14. 2010. 2007). the Center for Epidemiologic Studies Depression Scale (CES-D). and fed a diet 206 . "Concentration". and the Indefinite Complaints Index (ICI). 2007). While the results point towards a possible reduction of depression and anxiety in the study group with H. depression. erinaceus intake was significantly lower than at the start of the trial. Kawagishi and Zhuang. Hericium erinaceum (Pom Pom.Maitake mushroom extracts have been suggested to ameliorate progressive hypertension in female Sprague-Dawley rats via an effect on systolic blood pressure that may.

Both polysaccharides had significant antiartificial pulmonary metastatic tumour effects in mice with the polysaccharide from H. 207 . 2001). serum triglyceride and total cholesterol levels were more significant in the rats fed daily with the Hericium erinaceus extract at doses of 100mg/kg body weight rather than 20mg/kg body weight (Wang et al. and liver total cholesterol (28. laciniatum. The hypolipidemic effect of exo-polymers produced in submerged mycelial cultures of Hericium erinaceus (HE).9%). Phellinus pini (PP).. 2011).7%).. Yang et al. phospholipid (16. HE exo-polymer proved to be the most potent. compared to the saline administered (control) group. and Grifola frondosa (GF) has been investigated in dietary-induced hyperlipidemic rats. 2005). The effects on blood glucose.6%). Memory and learning function was examined. However. erinaceus and galactose in H. A hypolipidemic effect was achieved in all the experimental groups. A methanol extract of the fruiting bodies of Hericium erinaceus has been fed to rats and shown to result in a significantly lower elevation rate of blood glucose level than control rats. low-density lipoprotein (LDL) cholesterol (39. significantly reducing plasma triglyceride (28. 2006). total cholesterol (29. Auricularia auricula judae (AA). erinaceus over a 23-d experimental period.0%). Flammulina velutipes (FV). NF-kappaB (Son et al. 2002a)..containing H. with H. both of the polysaccharides enhanced the increase of T cells and macrophages (immuno-enhancing activity) (Wang et al. Immuno-regulatory functions of Hericium erinaceum have been demonstrated in an aqueous extract by a stimulation of inducible nitric oxide gene expression followed by nitric oxide production in macrophages via enhancement of activation of the transcription factor. erinaceus being more effective than that from H. 2003. The results demonstrated the potential of Hericium erinaceus exo-polymer in treating hyperlipidemia in dietary-induced hyperlipidemic rat (Yang et al. erinaceus preventing impairments of spatial short-term and visual recognition memory induced by the amyloid beta(25-35) peptide (Mori et al.9%) levels.. laciniatum. however... Polysaccharides from Hericium erinaceum and Hericium laciniatum have been extracted from culture broth and the polysaccharide components were mainly glucose in H. The animals were administered with exo-polymers at the level of 100mg/kg body weight daily for four weeks.

suggesting that H. 2010). Aqueous extracts of Hericium erinaceus (17. 2012).) pers. Administration of either the water-extract or ethanol-extract with a high fat diet for 28 days resulted in a marked decrease in body weight gain. protected against focal cerebral ischemia. 2010b).) Pers. 2011). 2010)..: Fr. A study in mice has reported that consumption of either a hot water extract or ethanol extract of Hericium erinaceus improved lipid metabolism in mice fed a high-fat diet..: Fr. an aqueous extract of the culinary-medicinal lion's mane mushroom.. Hericium erinaceus (Bull.. 2011). by increasing nerve growth factor levels. (Aphyllophoromycetideae) has been shown to accelerate wound healing in rats (measured as less scar width at wound enclosure with the healed wound containing fewer macrophages and more collagen with angiogenesis.. fat weight as well as blood and hepatic triacylglycerol levels (Hiwatashi et al... (Aphyllophoromycetideae) has also been shown to reduce ulceration in ethanol-induced gastric ulcers in rats (Mahmood et al. In Sprague Dawley rats.. acidic and alkaline extracts with similar proximate compositions were both inactive (Kim et al. compared to wounds dressed with sterilized distilled H2O (Abdulla et al. erinaceum and its components could be useful for preventing cerebral infarction (Hazekawa et al. Antiproliferative and HIV-1 reverse transcriptase inhibitory activities have been demonstrated from dried fruiting bodies of Hericium erinaceum (Li et al. Treatment of mice with Hericium erinaceum (300 mg/kg for 14 days) prior to middle cerebral artery (MCA) occlusion. 2008).Pretreatment with Hericium erinaceus (Bull. Hericium erinaceus mushroom-induced apoptosis of U937 human monocytic leukemia cell has been reported to be via an effect on cell proliferation that involves activation of mitochondria-mediated caspase-3 and caspase-9 but not caspase-8 (Sung Phil et al. 2011a). It is interesting to note that aqueous and aqueous/ethanolic extracts of Hericium erinaceus (Yamabushitake) mushroom were able to induce apoptosis in U937 human monocytic leukemia cells. however. 208 .7%) showed a relatively high Antioxidant Index (% relative to quercetin) in vitro (Abdullah et al.

Hypsizigus marmoreus (Buna-shimeji) have been reported.. The seven sterols and three polyisoprenepolyols were further evaluated for their inhibitory effects on Epstein-Barr virus early antigen (EBV-EA) activation induced by the tumour promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) in Raji cells. From the active fractions of the extracts. human 209 . but not as effective for Meth A fibrosarcoma. solid sarcoma 180 and syngeneic tumour and Meth A fibrosarcoma. and ergosterol markedly inhibited tumour promotion in a two-stage carcinogenesis experiment (Yasukawa et al. Chemical analysis revealed one of them to be beta-(1-3)-glucan with a significant inhibitory effect against tumour-growth of sarcoma 180 (Ikekawa et al.. Anti-tumour-promoting activity has been found in methanol and ethyl acetate extracts of the mushroom 'Buna-shimeji'. The isolates showed inhibitory activity against 12-O-tetradecanoylphorbol-13-acetate induced ear inflammation in mice. Two of the sterols showed a potent inhibitory effect while preserving the high viability of the Raji cells (Akihisa et al. isolated from the nonsaponifiable lipid fraction of the dichloromethane extract of Hypsizigus marmoreus. while the others were inactive. 1992). were isolated. Fractionation of anti-tumour substances of the aqueous extract isolated four polysaccharides. The aqueous extract was highly active in inhibiting growth of solid sarcoma 180. 1994). Six of the sterols and two of the polyisoprenepolyols showed a minimum inhibitory concentration (MIC) in the range of 1-51 mg/ml. two sterols. have been tested for their anti-tubercular activity against Mycobacterium tuberculosis strain H37Rv using the Microplate Alamar Blue Assay (MABA). Aqueous and methanol extracts of Hypsizigus marmoreus have been tested against allogeneic tumour.Hypsizigus marmoreus (Buna-Shimeji) Anti-tubercular activity and an inhibitory effect on Epstein-Barr virus activation of sterols and polyisoprenepolyols from an edible mushroom. Seven sterols and eight polyisoprenepolyols. Chloroform extracts of the fruit bodies of Hypsizigus marmoreus have been shown to exhibit moderate cytotoxicity towards cultured human colon carcinoma (HT-29). Hypsizigus marmoreus (Tricholomataceae). 2005).. ergosterol and ergosterol peroxide.

Hypsiziprenol A9 also decreased expression of phosphorylated retinoblastoma protein (ppRb). 2007). Anti-proliferative activities of fractions of Hypsizigus marmoreus have been examined using HepG2 cells in vitro. Oral administration of the fruit body of H..with antiproliferative activity against the L1210 leukemia cell line has also been purified (Guan et al. It was also suggested that the mushroom might play a role in the decrease of lipid peroxides through antioxidant activity induction (Matsuzawa. which were determined as thiobarbituric acid reactive substances. which inhibits the Lewis lung carcinoma cell adhesion to type IV collagen has been reported.and concentrationdependent manner by up to 80% on HepG2 cells by inducing arrest of the G1 phase.. marmoreus fruit body could induce an antioxidant effect. A type IV 210 .breast carcinoma (MCF-7) and human hepatoblastoma (HepG-2) cell lines (Xu et al. The methanol extract of H.. 2007). Proliferation of human leukemic U937 cells has been shown to be significantly inhibited by conditioned medium of human peripheral blood mononuclear cells stimulated with coldwater extracts (10-800 mg/mL of medium) of Hypsizigus mamoreus. 2006). These results showed that the intake of H. isolated from fruiting bodies of Hypsizigus marmoreus has also been shown to have antiproliferative activity against mouse leukemia cells and human leukemia and hepatoma cells (Lam and Ng. and cyclin E in a dose-dependent manner. A novel ribonuclease. The results suggested that hypsiziprenol A9 can inhibit the growth of HepG2 cells through inducing G1 phase cell cycle arrest due to the inhibition of pRb phosphorylation (Chang et al. and the increase of antioxidant activity in the plasma of tumour-bearing mice was an important mechanism in cancer prevention. cyclin D1. Hypsiziprenol A9 inhibited cell proliferation in a time.marmoreus markedly induced antiproliferative activity and an active compound from this mushroom has been identified as hypsiziprenol A9. 2005). 2004). Agrocybe aegerite and Flammulina velutipes (Ou et al. The isolation of a collagen-binding protein from Hypsizigus marmoreus. non-tumour-bearing and tumour-bearing mice. A thermostable ribosome-inactivating protein with a molecular weight of 20kDa. from fresh fruiting bodies of Hypsizigus marmoreus. The antioxidant effects of Hypsizygus marmoreus have been studied for peroxyl and alkoxyl radicals by ordinary. 2001). marmoreus exhibited potent anti-tumour or cancerpreventive effects and caused a significant decrease in lipid peroxide levels..

Hypsizigus marmoreus. Initial treatment with oral prednisolone was recommended for patients with high levels of total cell counts in bronchoalveolar lavage fluid (Tsushima et al. The use of a mask was ineffective for patients with a high serum Krebs von der Lungen-6 (KL-6). 2011). HM 23.collagen-binding protein of 23kDa was isolated from the mushroom. 2011). bound to type IV and type I collagens and gelatin. but not to laminin or bovine serum albumin. 2006).. 1995). suggesting their potential immunomodulating activities (Bao and You.. An evaluation of protective measures concluded that complete cessation was the best treatment for hypersensitivity pneumonitis.. TNF-alpha and IL-6 by inducing mRNA expression (Bao et al. Bunashimeji-related hypersensitivity pneumonitis has been reported in workers who cultivate this mushroom in indoor facilities in Japan. prostaglandin E2 as well as cytokines. such as IL-1 beta. 2012). A further study from the same group has subsequently also shown that alkalisoluble proteoglycans and acid-soluble proteoglycans from Hypsizygus marmoreus significantly stimulated Raw264. Water-soluble extracts isolated from Hypsizigus marmoreus have been shown to significantly stimulate Raw 264..7 cells to release nitric oxide.7 cancer cells to release nitric oxide (NO) and prostaglandin E(2). This protein. The adhesion of Lewis lung carcinoma cells was inhibited when the type IV collagen substratum was pretreated with HM 23 (Tsuchida et al. An extract from Hypsizygus marmoreus has also been shown to inhibit platelet aggregation induced by collagen suggesting that it may have an effect against platelet related cardiovascular disease (Park et al. surfactant protein-D (SP-D) concentration and severe ground-glass opacity on chest high-resolution computed tomography. and to much lesser extent to fibronectin. 211 .

24-dien-21-al. obliquus showed significant cytotoxic activity against the selected cancer cell lines (lung carcinoma A-549 cells. breast adenocarcinoma MCF-7 cells.Inonotus obliquus (Chaga) Anticancer activity of sub-fractions containing 3 betahydroxy-lanosta-8. of the Chaga mushroom (Inonotus obliquus) against human cancer cells and in Balbc/c mice bearing Sarcoma-180 cells has been reported. 2011).) isolated from I. and cervical adenocarcinoma HeLa cells) in vitro. Leccinum extremiorientale Two sterols isolated from the edible mushroom Leccinum extremiorientale have been shown to suppress the formation of osteoclasts and thereby may have some value in the treatment of osteoporosis (Choi et al. All of the subtractions isolated from I. To elucidate the mechanism of the cognitive enhancing activity of MEC. inotodiol and lanosterol. 2010).24dien-21-al. The significant cognitive enhancement observed in mice after MEC administration was closely related to higher brain anti-oxidant properties and inhibition of AChE activity (Giridharan et al. 2010). 212 . Subfraction I (3 beta-hydroxy-lanosta-8. obliquus showed greater inhibition of tumor growth than subtractions 2 and 3 (inotodiol and lanosterol) which agreed well with the in vitro results (Chung et al. anti-oxidant enzymes.. the activities of acetylcholinesterase (AChE). Cognitive enhancing and antioxidant activities of Inonotus obliquus (Chaga) have been evaluated against scopolamine-induced experimental amnesia in mice. stomach adenocarcinoma AGS cells. A methanol extract of Chaga (MEC) at 50 and 100 mg/kg doses was administered orally for 7 days to amnesic mice.. MEC treatment for 7 days significantly improved the learning and memory.. the levels of acetylcholine (ACh) and nitrite of mice brain homogenates were evaluated.

complement proteins and cytokines measured were not altered. and the number. and other blood chemistry) were not influenced by Lentinex (R). in 42 healthy. placebo-controlled trial (Gaullier et al.. crossover. The number of NK cells increased significantly in both groups. 2011). while for the gingival index significant differences were found for both mushroom versus placebo and mushroom versus Listerine. 2011). then after a washout period of 4 weeks. The effect and safety of a soluble beta-glucan from Lentinus edodes mycelium. 2011). Lentinex consists of approximately 98 % water and 2 % dry matter (beta-glucan lentinan. A fraction from Shiitake has also been shown to have a strong inhibiting effect on dentin demineralization and induce microbial shifts that could be associated with oral health (Zaura et al. Lentinex given orally to elderly subjects was deemed to be safe and induced an increase in the number of circulating Bcells (Gaullier et al. The immunoglobulins. Statistically significant differences were obtained for the plaque index on day 12 in subjects treated with mushroom versus placebo. 2011) where two groups were given either 2. free glucose and N- 213 .. The data suggest that this mushroom extract may prove beneficial in controlling dental caries and/or gingivitis/periodontitis (Signoretto et al. but there was no significant difference between the groups.. and severity of adverse events were similar to placebo. The changes in the number of B-cells were significantly different between the groups.5 mg/day Lentinex (R) orally or placebo for 6 weeks. liver function.. the alternate supplementation was given for 6 weeks. Decreases in total bacterial counts and in counts of specific oral pathogens were observed for both mushroom extract and Listerine in comparison with placebo. an aqueous mycelial extract of Lentinula edodes (Shiitake mushroom).Lentinula edodes (Shiitake) A clinical trial in 30 volunteers has been undertaken over 11 days in which a low molecular mass fraction of an aqueous extract of Lentinus edodes (Shiitake) was evaluated as an oral mouthrinse. kidney function. The safety blood variables (differential cell count. as a novel food ingredient in the context of Regulation (EC) No 258/97. The mushroom extract was evaluated against Listerine and a placebo (water). The European Food Safety Authority (EFSA) has recently carried out a safety assessment for Lentinex. Lentinex (R). nature. elderly subjects has recently been evaluated in a double blind.

containing constituents).7 mug/kg body weight for a 60 kg person. The effects of diets containing dry powdered Shiitake mushroom on frequency of azoxymethane-induced colon aberrant crypt foci (ACF) and intestinal tumours in male Sprague-Dawley rats have been studied. they were supporting but of limited value regarding a safety assessment. The intake of beta-glucan resulting from the proposed use is low compared to the intake estimated from the consumption of the mushroom Lentinula edodes and of other beta-glucan sources. Furthermore. The proposed intake of 2. mycelial extracts did not induce any cytostatic effect in both cancer and normal cell lines based on a DNA synthesis assay. EFSA noted the presence of soy peptides in the culture medium.. However. this activity has been shown to be host-mediated and not by direct cytotoxic activity to cancer cells.5 mL Lentinex containing 1 mg lentinan (beta-glucan)/mL corresponds to 41. 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. 2008) has now demonstrated cytotoxic and cell growth inhibitory (cytostatic) effects of aqueous extracts of the mushroom on the MCF-7 human breast adenocarcinoma cell line. (Liu et al. The animal and human studies provided by the applicant to EFSA were primarily carried out to determine the efficacy of the novel food ingredient. adverse effects reported after the consumption of the fruiting body of the Shiitake mushroom were not considered relevant. 2009). Although an allergenic risk cannot be excluded for sensitive subjects. Protein extracts of Lentinus edodes C91-3 fermentation broth administered to mice with cervical cancer prolonged the lifespan of tumour-bearing mice significantly and killed cervical cancer U14 cells in vitro. Pregnant rat dams and their progeny were fed 214 . The effect was demonstrated with fruit body and mycelial extracts. Extracts from Lentinula edodes (Shiitake) have been widely reported to have anti-tumour activity. The safety of Lentinex as a novel food ingredient was established at the proposed conditions of use and the proposed levels of intake (EFSA Panel on Dietetic Products and Allergies. A recent study (Israilides et al. Owing to the fermentative production of the novel food ingredient from the mycelium and the final application of a heat-induced sterilisation step in various food products. the difference being that there was no significant suppression on normal cells with the latter. In addition to the direct inhibition of the proliferation of human breast cancer cells in vitro. 2010). the Lentinula edodes extract had immunostimulatory properties in terms of mitogenic and co-mitogenic activity in vitro. EFSA concluded that such a risk was expected not to be higher than that resulting from the normal consumption of the fruiting body of Lentinula edodes..

. The data demonstrated a weightcontrolling and hypolipidemic effect of both A-PBP and L-PBP via a mechanism involving absorption of cholesterol (Kweon et al.05 to 0. 2007). control diet) or casein supplemented with Shiitake (1% or 4% wt/wt). Shiitake at 4% intake elicited a reduction in colon tumour multiplicity. Casein. whereas those fed the 4% Shiitake diet were of slightly reduced body weight. Aberrant crypt foci and tumours were most prevalent in the mid and distal regions of the colon. the number of lymphocytes yielded by the small intestine increased by up to 40% and tumour cytotoxicity against P815 cells and cytokine production was also augmented.AIN-93G diets containing casein (20%. Shiitake extracts have been dispersed with lecithin micelles to prepare superfine particles (0. on serum cholesterol and body weight have been investigated in 90 female volunteers.3-glucan (micellary mushroom extracts). In contrast. The animals of the autolyzed-LE group showed significantly lower blood pressure compared to the control or LE group.. The effect of Shiitake (Lentinus edodes. When mice were fed with these micelles of beta-glucan (0.2 microns in diameter) of beta-1. The 4% Shiitake diet elicited increased active energy expenditure and reduced adiposity of rats. extracted from the mycelia of Agaricus blazei and Lentinus edodes. the inhibitory actions of 4% Shiitake mushroom on the indices of rat colon tumourigenesis where statistically validated (Frank et al. The effects of protein-bound polysaccharides (A-PBP and L-PBP). The authors suggested a stimulatory action of 1% Shiitake on rat colon tumourigenesis which is puzzling as the data were not statistically significant.(fermented-) Shiitake (autolyzed-LE) on blood pressure and serum fat levels of spontaneously hypertensive rats (SHR) have been studied. However. Small bowel and colon tumours and colon ACF were evaluated in the male progeny at 18 weeks after azoxymethane treatment. LE) and autolyzed. suggesting that smaller amounts of micellary beta-glucan might be useful for the potentiation of intestinal immunity (Shen et al. 2006). smaller amounts of beta-glucan).and 1% Shiitake-fed rats exhibited identical growth curves. The serum levels of total cholesterol (TC). triglyceride and phospholipid of the groups fed with LE and autolyzed-LE 215 . 2009). The Shiitake mushroom-derived immuno-stimulant lentinan has also been reported to protect against murine malaria blood-stage infection by evoking adaptive immune-responses (Zhou et al..75mg/day/mouse.. Shiitake intake had no effect on the relative incidence of tumours in the colon or small intestine (duodenum). Consumption of 1% Shiitake stimulated growth of invasive adenocarcinomas in the mid colon and favoured a non-significant increase in median frequency of ACF in this same region. 2002).

2000). The results demonstrated that mushroom fiber lowered the serum total cholesterol level by enhancement of the hepatic low density lipoprotein (LDL) receptor mRNA (Fukushima et al. Le-A. An inhibitory activity of the angiotensin I-converting enzyme (ACE) was compared between of LE and autolyzed-LE.3(R)-dihydroxy-4-(9-adenyl)-butyric acid. were investigated. 2001). The Shiitake strains under investigation exhibited up to 10-fold higher levels of eritadenine than previously reported for other Shiitake strains. The changes in the content of an anti-tumour polysaccharide from Lentinus edodes (lentinan) during storage have been investigated. but the content decreased markedly at higher temperature (20ºC) (Mizuno. Le-1. The Shiitake mushroom (Lentinus edodes) contains the hypocholesterolemic agent eritadenine. Methanol extraction was used to recover as much eritadenine as possible from the fungal cells. 2(R). Methanol and water extracts from Lentinus edodes have been shown to have antioxidant activity against lipid peroxidation of rat brain homogenate. The antioxidant activity against 216 .. and enzymes that degrade the fungal cell walls were also used to elucidate if the extraction could be further enhanced.. A study has recently been conducted to quantify the amount of the cholesterol reducing agent eritadenine in Shiitake mushrooms.were lower than those of the control group. It was suggested that the serum TC decline is the action of eritadenine that is contained in the Shiitake mushroom. and atherogenic index [(TC-HDL-C)/HDL-C] improved significantly in 21 days. Plasma cholesterol concentration in rats has been shown to be reduced by feeding of mushroom Shiitake (Lentinus edodes) fiber. When the mushrooms were stored at low temperature. 2002). The amounts of eritadenine in the fruit bodies of four different shiitake mushrooms. the content of their anti-tumour polysaccharides showed hardly any changes. Autolyzed-LE showed higher inhibitory activity than LE against the ACE. Pre-treatment of mushrooms with hydrolytic enzymes before methanol extraction resulted in an insignificant increase in the amount of eritadenine released. The results suggested the potential for delivery of therapeutic amounts of eritadenine from the ingestion of extracts or dried concentrates of Shiitake mushroom strains (Enman et al. 2007). The results suggested that the hypotensive action of autolyzed-LE was due to concomitant ACE inhibitory activities of peptides and gamma-aminobutyric acid contained in higher amounts during the autolysis of LE (Watanabe et al. and Le-B. Le-2..

After heat treatment. Shiitake mushroom extract has also been reported to have anti-tumour effects on prostate cancer (Hackman et al.2-Azino-bis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical and 1... Among log-grown Shiitake.9-fold compared to that in the extract from the raw sample. A study has been conducted to determine if management protocols influence the HMWP of Shiitake (Lentinula edodes (Berk. in Shiitake mushrooms may promote human health. The results also indicated that log-grown Shiitake contained more HMWP than did substrategrown Shiitake. one 217 . The effect of heat treatment on the changes in the overall antioxidant activity and polyphenolic compounds of Shiitake extract has been investigated. including lentinan. High-molecular-weight polysaccharides (HMWP). 2006a).) Pegler) mushrooms. respectively.2-fold compared to the raw sample. ethanol-insoluble polysaccharides was a simple way to estimate HMWP. A high genistein. Supplemental amounts of a polysaccharide/oligosaccharide complex obtained from a Shiitake mushroom extract have been evaluated for the ability to lower the prostatespecific antigen level in patients (n=62) with prostate cancer. 2. The free polyphenolic content in the extract heated at 121ºC for 30 min was increased by 1. An ethyl acetate fraction from Shiitake (Lentinus edodes) mushrooms has been investigated using two human breast carcinoma cell lines (MDA-MB-453 and MCF-7). The data showed that the Shiitake mushroom extract alone was ineffective in the treatment of clinical prostate cancer (White et al. The data showed that heat treatment significantly enhanced the overall antioxidant activities of Shiitake mushrooms (Choi et al. 2001). the free and bound polyphenolics and flavonoids in the mushroom extracts were analyzed. 2002). The ABTS and DPPH radical scavenging activities were increased by 2. 2002). The results indicated that measuring the total carbohydrate content of waterextractable..1-diphenyl-2picrythydrazyl (DPPH) radical scavenging activities were measured to evaluate antioxidant activity of the extracts..0-fold and 2.lipid peroxidation was found to correlate with the phenolic content in different sub-fractions of the mushroom extracts (Cheung and Cheung. 2005). The results suggested that there is considerable variation among Shiitake mushrooms in HMWP content and that production protocols influenced the HMWP content of mushrooms (Brauer et al. Raw Shiitake was heated at 100 and 121ºC for 15 or 30 min using an autoclave. both mushroom strain and tree species influenced HMWP content. The polyphenolic contents and antioxidant activities in the extracts increased as heating temperature and time increased.

human non-malignant breast epithelial cell line (MCF-10F). The data suggest that inhibition of growth in tumour cells by the Shiitake mushroom extract may result from an induction of apoptosis (Fang et al. The anti-microbial activity of the culture fluid of Lentinus edodes mycelium grown in submerged liquid culture has been demonstrated against Streptococcus pyogenes. Concentration-dependent anti-proliferative effects of the fraction were observed in all cell lines. The active compounds were detected by preparative thin layer chromatography. Extracts from fermentation broth and mycelium of 15 strains of Lentinus edodes have been shown to be active against gram positive and gram negative bacteria. non-malignant cells were less sensitive to the fraction for the suppression of cell growth and regulation of bax. p21. 2006). A 51% anti-proliferative effect occurred at the highest concentration of the fraction (800mg/L). KS-2 suppressed the growth of EHRLICH as well as Sarcoma-180 tumours in mice when given either orally or intraperitoneally (Fujii et al. Two were identified with UV. The substance responsible for the activity was heat-stable and was suggested to be lenthionine. 2006).. Strains of L. 218 ..and mass spectrometry as lentinamycin B and erytadenine (lentinacin). edodes strains (Soboleva et al. Cell cycle analysis revealed that the fraction induced cell cycle arrest by a significant decrease of the S phase. Compared to malignant tumour cells. KS-2. The strains differed by the set of the organisms susceptible to the action of the extracts. Lentinamycin B was found to be the main component responsible for the anti-bacterial activity of the L. Approximately 50mg/L of the fraction induced apoptosis in 50% of the population of four human tumour cell lines and the fraction-induced apoptosis may have been mediated through the pro-apoptotic bax protein which was up-regulated. an anti-bacterial and antifungal sulphur-containing compound (Hatvani. 2001). yeasts and mycelial fungi. including dermatophytes and phytopathogens. extracted from culture mycelia of Lentinus edodes has also been reported. The isolation and characterization of an anti-tumour polysaccharide. edodes combining marked anti-bacterial properties and high yields of water soluble polysaccharides were screened. Staphylococcus aureus and Bacillus megaterium. which was associated with the induction of cdk inhibitors (p21) and the suppression of cdk4 and cyclin D1 activity.. 1978). and cdk4 expression. cyclin D1. and two myeloma cell lines (RPMI-8226 and IM-9).

Much smaller tumours were formed in nude mice inoculated with lymphocytes. Six established human colon-carcinoma cell lines segregated into three groups of different degrees of differentiation were used in this study. Follow-up investigation proceeded with the use of nude mice (athymic). in contrast to the larger tumour formed in nude mice without lymphocyte inoculation.A study on the action of lentinan (extracted from Shiitake mushrooms (Lentinus edodes) has been conducted using murine lymphoma (K36) cells in a AKR mouse model. A subsequent study by the same group. and increased plasma insulin by 219 . and triglyceride (TG) levels were observed in rats fed with Lentinus edodes and Cordyceps militaris EPs. 2001). Further investigation on the effectiveness of the extracted lentinan was then performed using human colon-carcinoma cell lines in mice. total cholesterol (TC). Plasma glucose and TC were also reduced by administration of Phellinus linteus EPs. This was then followed by inoculation of the human colon-carcinoma cell lines into these mice.. Significant regression in tumour formation was observed in prefed mice compared to control (unfed) mice when K36 or human colon-carcinoma cells were used. 2002). The EPs of the three mushroom species also demonstrated a marked reduction in the level of plasma glutamate-pyruvate transaminase (GPT). but the TG level was not changed significantly. were able to retard the development of tumours in these mice (Ng and Yap. Significant reductions in the size of the tumours were observed in mice prefed with lentinan. The hypoglycemic effect of exo-polymers (EPs) produced from submerged mycelial cultures of five varieties of mushrooms on streptozotocin (STZ)-induced diabetic rats have been investigated. One group was not fed (control) and the second group was prefed with lentinan for 7 days prior to inoculations with the cancer cells. The result demonstrated the hypoglycemic activity of EPs of three mushroom varieties in STZ-induced diabetic rats and suggests some potential in the control of diabetes mellitus (Kim et al. The size of the tumours that developed was rated after 1 month. "primed" lymphocytes. Significant reductions in plasma glucose. using higher concentrations (200mg/kg body weight in streptozotocin-induced diabetic rats) of exo-polymers from a submerged mycelial culture of Lentinus edodes has shown that the administration of the exo-polymer reduced the plasma glucose level by as much as 21. The five experimental groups were fed with EPs (50mg/kg body weight) for 7 days. when given passively to immuno-deficient mice. The study concluded that the anti-tumour property of lentinan was maintained with oral administration. Lymphocytes extracted from AKR mice prefed with lentinan for 7 days were inoculated into the nude mice.5%. In addition.

...22. A study has been conducted with 10 people where each participant ingested 4g of Shiitake powder daily for 10 weeks (trial 1). It was also shown to lower the plasma total cholesterol and triglyceride levels by 25. were relatively resistant to these compounds. increased eosinophil granule proteins in serum and stool. coli M-17.. Staphylococcus spp. Prevotella spp. Symptoms and eosinophilia resolved after discontinuing Shiitake ingestion. of oral origin.. other general bacteria. 2002c). Enterococcus faecalis. Escherichia spp. edodes) at a concentration of 5% from the volume of the nutrient medium was found to produce a pronounced anti-microbial effect with respect to Escherichia coli O-114. Lactobacillus spp.. but in contrast to the previous reports in Japan. and it has been suggested that this dermatitis may be photosensitive as nearly half of the patients studied developed the dermatitis on skin exposed to sunlight (Hanada and Hashimoto. Gastrointestinal symptoms coincided with eosinophilia in two subjects. A study in Korea has also reported dermatitis effects.. cases with Shiitake dermatitis occurred after eating boiled or cooked Shiitake mushrooms suggesting that a non-thermolabile factor/component may be involved (Ha et al. and increased gastrointestinal symptoms (Levy et al. In contrast. 1998). Bacillus spp.5%. Candida albicans and to stimulate the growth of E. edodes juice (Kuznetsov et al.. such as Enterococcus spp. The action of the juice of Shiitake mushrooms (L. respectively (Yang et al.000mg/kg has been given to 5 Crj:CD(SD) IGS strain of rats of each sex for 1 220 . A single oral dose of an extract of cultured Lentinus edodes mycelia. at dosage levels of 500 and 2..1% compared to the control group. and Porphyromonas spp. 2005). and Candida spp.. and the protocol was repeated in the same subjects after 3 to 6 months (trial 2). The anti-bacterial activity of chloroform extracts and ethylacetate extracts were relatively heat-stable...1 and 44. Actinomyces spp. ethylacetate or water from dried Shiitake mushrooms (Lentinus edodes) have been reported which possessed efficient anti-bacterial activities against Streptococcus spp. The authors reported that daily ingestion of Shiitake mushroom powder in five of 10 healthy persons provoked blood eosinophilia. Three anti-bacterial compounds extracted by chloroform. Staphylococcus aureus. 1998). while the water extract was heat-labile (Hirasawa et al. Bifidobacteria and Lactobacteria exhibited resistance to the action of L. Shiitake dermatitis after the ingestion of raw Shiitake mushrooms has been reported.. primarily in Japan. 2003). 1999).

The no observed adverse effect level (NOAEL) of L.E.15 +/. No effects of Lentinus edodes mycelia were reported in either sex by body weight measurement or necropsy finding (Koike et al. necropsy finding.. urinalysis.M. The study reported no clinically significant changes related to toxicity. in an artificial mouth model (constant depth film fermenter). WBM. WBM and SM tended to reduce the CIA index from 5. A follow on study by the same authors that extended the treatments for 28 days reported no effects in either sex by body weight measurement.M. No mortality or abnormality in the general status or appearance was observed in rats administered L. 2002a). blood chemical analysis. Whereas 58% of control mice had a CIA index 7. organ weight measurement.. The total bacterial numbers as well as numbers of eight key taxa in the oral environment were investigated over time. unlike chlorhexidine which had a limited effect on all taxa (Ciric et al. Compared to the control diet.0.06) (median.82 to 3. The results indicated that Shiitake mushroom extract lowered the numbers of some pathogenic taxa without affecting the taxa associated with health.. ophthalmological examination. extract was considered to be more than 2. antiadhesion/coaggregation. suggesting that these LMM fractions could modulate the effects of bacteria associated with periodontal disease in gingival cells (Canesi et al.) has been determined using repeated doses (2.11 +/0. Furthermore. a study has compared the effectiveness of Shiitake mushroom extract against the active component in a leading gingivitis mouthwash.95 (P = 0.E. The toxicological safety of an extract from cultured Lentinula edodes mycelia (L. Low molecular mass (LMM) fractions from extracts of Shiitake mushrooms (as well as from raspberry and red chicory) have been shown to be a useful source of specific antibacterial. The effects of white button mushrooms (WBM) and shiitake mushrooms (SM) on collageninduced arthritis (CIA) have been studied in 8-wk-old female dilute brown non-agouti mice. 2011). Although both types of mushrooms reduced plasma TNF alpha (34%. Each of the LMM fractions tested prevented or reduced the induction of gene expression of the periodontal pathogens Prevotella intermedia and Actinomyces naeslundii.M extract. and antibiofilm agent(s) that may be used for protection towards caries and gingivitis. No abnormal signs were noted in either sex of any group. 2002b). food consumption measurement. 221 ..day. 2011).E. The control group was treated with water by injection. 6-9 to 1-2) 31 d post-collagen injection.. containing chlorhexidine. 2010).000 mg/kg/day) to male and female Wistar rats for 28 days. only 23% of WBM and 29% of SM mice did (P = 0. and its toxicity was examined. or histopathological examination (Koike et al.000 mg/kg/day (Yoshioka et al. hematological examination.1).

3-fold (P < 0. have also been shown to have a hepatoprotective effect on CCl4--induced liver injury in mice. 2 times/week).05) (Chandra et al.. only SM increased plasma IL-6 by 1. SM). plasma triglyceride. suppressed collagen accumulation and significantly decreased hepatic hydroxyproline content. Combined therapy of Lentinan and S-1 markedly exerted antitumor effects on human OSCC xenografts and significantly induced apoptotic cells in tumors treated with Lentinan plus S-1.64%. It should be noted however. 2010). and total fat mass (Handayani et al. 222 . Supplementation of rats on a high fat diet with Shiitake Mushroom (Lentinus edodes) powder resulted in negative correlations between the amount of Shiitake mushroom supplementation and body weight gain. and further studies are needed to confirm such effects...9 mg/kg/day. The responses of human oral squamous cell carcinoma (OSCC) cells to Lentinan. which is the quantitative marker of fibrosis. 2011b). 2011) Strong antioxidant properties have recently been described for a water-extractable polysaccharide fraction from Lentinus edodes (Shiitake) (Chen et al. The intravenous administration of syringic acid and vanillic acid significantly decreased the levels of the transaminases. The phenolic compounds. 2011a). 2012a). which play a central role in liver fibrogenesis. While these data provide some suggested benefits in this animal model.. 2010). with no loss of body weight being observed in mice treated with the combined therapy (Harada et al. syringic acid and vanillic acid from Lentinula edodes mycelia that have radical scavenging activity. that another study has suggested that supplementing a mouse diet with 5% SM can result in a fatty liver (an elevation in IL-6 is also implicated in fatty liver disease).. an oral antineoplastic agent that can induce apoptosis in various types of cancer cells (6. beta-(1 -> 3)-D-glucan. and maintained hepatocyte viability. This effect of SM was not seen with WBM consumption (Chandra et al. Both of these compounds inhibited the activation of cultured hepatic stellate cells. liver histology was completely normalized. statistical validation of these data is borderline. 7 times/week)has been studied using a nude mouse xenograft model. alone and in combination with S-1.. Syringic and vanillic acid may therefore play a role in the suppression of hepatic fibrosis in chronic liver injury (Itoh et al. but 15 days post withdrawal of SM. an extract from Lentinus edodes (0.1 mg/kg/day.

and this in vivo anti-tumor effect was not observed in nude mice. A combination of lentinan with standards of care in acute myeloid leukemia. monocytes and circulating cytotoxic T-cells..Letinus edodes has been shown to have immunomodulating effects which are mediated via the enhancement of type-1 helper T cell-mediated cellular immunity (Hyun Ji et al. idarubicin. Lentinan. Intake of Lentinula edodes mycelia extract significantly inhibited tumor growth in C57BL/6 mice inoculated with B16 melanoma. and cytarabine increased average survival compared with monotherapy and reduced cachexia suggesting that nutritional supplementation of cancer patients with lentinan would warrant investigation (McCormack et al.... 223 . 2011). BN rats supplemented daily with lentinan exhibited weight gains.. and had a reduction in anti-inflammatory cytokines IL-4. 2011). 2010). and IL-6.. as have the pharmacological activity and therapeutic applications of Lentinus edodes (Bisen et al. a cell wall beta-glucan from the fruiting bodies of Lentinus edodes has been reported to exert its immunomodulating activity (in RAW 264. 2011). possibly via a mitigation of T cell-mediated immunosuppression (Tanaka et al.7 macrophages) by activation of MAPK signaling pathways without secretion of TNF-alpha and NO (Xu et al. The effects of a beta-glucan supplement (Lentinan) from Lentula edodes (Shiitake) on BN rats have been studied and in a preclinical model of acute myeloid leukemia. Oral ingestion of Lentinula edodes extract restored immune responses of class I-restricted and melanomareactive CD8(+) T cells in these melanoma-bearing mice. A laccase with HIV-1 reverse transcriptase inhibitory activity has recently been isolated from fresh fruiting bodies of Lentinus edodes (Shiitake)(Sun et al. IL-10.. 2011) The effects of Active Hexose Correlated Compound (AHCC) from Lentinula edodes and its use as a complementary therapy in patients with cancer has recently been reviewed (Shah et al. increased white blood cells. 2011a). suggesting a T cell-dependent mechanism. 2010).

2011b).1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging assay. including the absolute stereochemistry of beta-hydroxyergothioneine. induces apoptosis and cell cycle arrest of human hepatocellular carcinoma Hep3B cells by modulating ERK phosphorylation. Structural determination. Serum IL-2 and IL-18 were significantly increased in the Sarcoma 180 implanted mice fed with the endopolysaccharide at 500 mg/kg and 250 mg/kg compared with those in control. N-hydroxy-N'.N'-dimethylurea. and increased the life span. Betahydroxyergothioneine showed the greatest protective activity against carbon tetrachlorideinduced injury in primary culture hepatocytes (Kimura et al. beta-hydroxyergothioneine has been isolated from the mushroom Lyophyllum connatum. Hispolon-induced S- 224 . 2005). Phellinus igniarius Oral administration of an endo-polysaccharide of Phellinus igniarius inhibited the growth of Sarcoma 180 and Hepatoma 22 cells that were implanted in mice. was achieved by spectroscopic analysis and X-ray crystallography. Ergothioneine.. based on a 1. and connatin (N-hydroxy-N'. through the induction of cell cycle arrest at S phase measured using flow cytometric analysis and apoptotic cell death. The concentrations of serum IL-2 only were significantly increased in Hepatoma 22 implanted mice using the same doses (Chen et al. Hispolon inhibited cellular growth of Hep3B cells in a time-dependent and dose-dependent manner. The radical scavenging activity of betahydroxyergothioneine was almost the same as that of ergothioneine. Hispolon. suggesting that the anti-tumor effect was mediated via enhancement of cell mediated immunity.N'-dimethylcitrulline) were also isolated.Lyophyllum connatum A new ergothioneine derivative.. All the compounds displayed the ability to scavenge free radicals. an active phenolic compound of Phellinus igniarius.

Ethanol extracts of Phellinus linteus have been shown to have antioxidant activities comparable to Vitamin C in scavenging the stable free radical 1. 2010).1-diphenyl-2-picrylhyrazyl (DPPH)..phase arrest was associated with a marked decrease in the protein expression of cyclins A and E and cyclin-dependent kinase (CDK) 2. 2011. Inhibitors of ERK (PB98095). The mycelial extract-adjuvanted vaccines were shown to confer cross-protection against variant H5N1 influenza viruses (Ichinohe et al. p38 MAPK. but not those of JNK (SP600125) and p38 MAPK (SB203580). Phellinus linteus has been reported to sensitise apoptosis induced by doxorubicin (an anticancer drug) in prostate cancer LNCaP cells suggesting that Phellinus linteus may have therapeutic potential to augment the magnitude of apoptosis induced by anti-prostate 225 . suppressed hispolon-induced S-phase arrest and apoptosis in Hep3B cells. 2011). Hispolon treatment also activated JNK.. The extracts also inhibited lipid peroxidation (LPO) in a concentration-dependent manner.. Exposure of Hep3B cells to hispolon resulted in apoptosis as shown by caspase activation. and ERK expression. 2003). and DNA fragmentation. Hispolon has also been shown to suppress SK-Hep1 human hepatoma cell metastasis by inhibiting matrix metalloproteinase-2/9 and urokinase-plasminogen activator through the PI3K/Akt and ERK signaling pathways (Huang et al... These findings establish a mechanistic link between the MAPK pathway and hispolon-induced cell cycle arrest and apoptosis in Hep3B cells (Guan-Jhong et al. The study also reported anti-angiogenic activities of Phellinus linteus (Song et al. Phellinus linteus Extracts of mycelia derived from Phellinus linteus have recently been tested as adjuvants for intranasal influenza vaccine. 2010b). PARP cleavage. The adjuvant effects of extracts of mycelia were examined by intranasal coadministration of the extracts and inactivated A/PR8 (H1N1) influenza virus hemagglutinin (HA) vaccine in BALB/c mice. Huang et al. with concomitant induction of p21waf1/Cip1 and p27Kip1.

... These results suggest that Phellinus linteus has two anti-metastatic functions . 2006a). Phellinus linteus has also been shown to mediate cellcycle arrest at a low concentration and apoptosis in response to a high dose in mouse and human lung cancer cells (Guo et al. 2007). 2005). and in particular. Phellinus linteus has been reported to contain constituents that exhibit potent anti-tumour effects through activation of immune cells.cancer drugs (Collins et al. 2010). angiogenesis and invasive behaviour of breast cancer cells (Sliva et al. the extracellular matrix. 226 . and directly inhibit cancer cell adhesion to.it acts as an immuno-potentiator and as a direct inhibitor of cancer cell adhesion (Han et al. 2006)..linteus contain anti-allergic and immuno-potentiating properties (Inagaki et al. 2005).. while hispolon extracted from Phellinus linteus has been shown to have antiproliferative effects in breast and bladder cancer cells (Lu et al. An extract from Phellinus linteus has been shown to have anti-inflammatory activity (Kim et al.. the stromal component of the prostate increased significantly by 80%. 2006).. A suppression of transforming growth factorbeta1 expression by 56% was observed with the mushroom extract treatment. and invasion through. A Phellinus linteus extract has also recently been reported to sensitize advanced prostate cancer cells to apoptosis in athymic nude mice (Tsuji et al.. 2008). It was found that the mushroom extract enlarged the prostate and therefore administration of Phellinus linteus extract should be considered carefully by those with an enlarged prostate (Shibata et al.. 2004a) via mediation of heme oxygenase-1 in an in vitro inflammation (macrophage) model (Kim et al. In addition. A study in mice has reported that boiling water soluble fractions from mycelium of P. Phellinus linteus has also been shown to suppress growth. the authors reported that PL increased macrophage NO production. The effect of a mushroom extract of Phellinus linteus on non-cancerous prostate cells using an experimentally developed rat benign prostatic hyperplasia model has been studied.. 2009). but that it had no direct effect on cancer cell growth. The results showed that prostate weight increased significantly by 37% owing to treatment with the mushroom extract. An acidic polysaccharide from Phellinus linteus has been shown to markedly inhibit melanoma cell metastasis in mice.

linteus extract inhibits viral glycoprotein expression on cell surfaces through inhibition of trafficking processes rather than glycoprotein synthesis (Doseung et al. 80% of the NOD mice had developed diabetes by 24 weeks of age. Intracellular reactive oxygen species scavenging activity of hispidin was approximately 55% at a concentration of 30 M. a viral glycoprotein. hispidin was shown to inhibit hydrogen peroxideinduced apoptosis and increased insulin secretion in hydrogen peroxide-treated pancreatic beta-cells indicating that hispidin may have anti-diabetogenic properties via protection of pancreatic beta-cells from reactive oxygen species in diabetes (Jang et al. In this study.Phellinus linteus -treated NOD mice developed diabetes. and angiogenesis via the inhibition of Wnt/beta-catenin signaling in SW480 human colon cancer cells (Song et al. superoxide radicals. in virusinfected baby hamster kidney cells. Phellinus linteus has been reported to inhibit tumor growth. invasion. A methanol extract of Phellinus linteus has been reported to inhibit the trafficking process of Newcastle disease virus hemagglutinin-neuramidase. 2011).. IL-2. The results suggested that P.. These data suggest that this polysaccharide isolated from Phellinus linteus inhibits the development of autoimmune diabetes by regulating cytokine expression. 2010). In a rat model of permanent focal cerebral ischemia (using Sprague-Dawley rats). The polysaccharide inhibited the expression of inflammatory cytokines. A 227 . including IFN-gamma.. The polysaccharide did not prevent streptozotocininduced diabetic development in ICR mice. and hydrogen peroxide in a dose-dependent manner. but none of thepolysaccharide. but up-regulated IL-4 expression by Th2 cells in NOD mice. Extracts from Phellinus linteus have also been shown to induce proapoptotic effects in the human leukemia cell line K562 (Shnyreva et al.. Histological examination of the pancreatic islets revealed that most of the islets isolated from treated mice were less infiltrated with lymphocytes compared with those of control mice. and TNF-alpha by Th1 cells and macrophages. a filtrate of Phellinus linteus broth significant reduced cortical infarct volume 30 and 60 minutes before onset of cerebral ischemia compared with the control group.. Hispidin from Phellinus linteus exhibited quenching effects against DPPH radicals. 2010a). 2011).A polysaccharide isolated from Phellinus linteus has also recently been reported to inhibit the development of autoimmune diabetes in non-obese diabetic (NOD) mice (Kim et al. In addition. 2010c). while post-treatment (30minutes after ischemic onset) also significantly reduced cortical infarct volume.

An earlier study from the same group at the same doses of PPC-Pr had reported its effect on alleviating gamma radiation-induced toxicity in the Swiss albino mouse model (Joseph et al. 2011)... 2011).significant benefit of this neuroprotective effect was a wide therapeutic time window since significant infarct volume reduction was obtained by administration. even after the ischemic event (Suzuki et al. The effects of A Phellinus linteus as a complementary therapy in patients with cancer has been reviewed (Sliva. 2010). It has recently been demonstrated that polysaccharides from Phellinus linteus (PL) inhibit proliferation and colony formation of HepG2 and that the growth inhibition of HepG2 cells was mediated by S-phase cell cycle arrest. Phellinus rimosus A polysaccharide protein complex (PPC-Pr) isolated from the mushroom Phellinus rimosus has been shown to have a protective effect (at doses of 5 and 10 mg/kg body weight intraperitoneally for 5 days consecutively) against oxidative stress induced by gamma radiation (4 Gy) in Swiss albino mice. PPC-Pr treatment enhanced the declined levels of antioxidants and demonstrated a DNA protective effect (as determined by a Comet assay) as well as significantly increasing the survival rate of animals (Joseph et al. Phellinus linteus also markedly inhibited cancer cell adhesion and invasion of the extracellular matrix and PL-induced apoptosis was associated with a reduction in B-cell lymphoma 2 levels and an increase in the release of cytochrome c.. 2012). The results suggest that PL exerts a direct antitumor effect by initiating apoptosis and cell cycle blockade in HepG2 cells (Wang et al. 2012a). 228 ..

. 40. Pholiota nameko (Nameko) A polysaccharide (20. Hypersensitivity pneumonitis to spores of Pholiota nameko has been reported in a mushroom farmer. and IFN-gamma..Phellinus robustus It has been reported that melanins from the medicinal mushroom Phellinus robustus have high antioxidant and geno-protective properties (Babitskaya et al.. 1996). 2007). Pleurotus citrinopileatus have been 229 . which subsequently inhibited the growth of U937 human myeloid leukemic cells (Chen et al. resulted in the symptoms and inflammatory effects quickly subsiding (Inage et al. and 60 mg/kg orally) isolated from Pholiota nameko has recently been shown to have a hypolipidemic effect Wistar rats(Li et al. Pleurotus citrinopileatus A nonlectin glycoprotein (PCP-3A) isolated from the fruiting body of the edible golden oyster mushroom Pleurotus citrinopileatus has been shown to stimulate human mononuclear cells to secrete cytokines TNF-alpha. although separation from the antigen along with corticosteroid therapy. 2010a). IL-2.. Anti-inflammatory effects of a bioactive nonlectin glycoprotein (PCP-3A) isolated from the fresh fruiting body of the golden oyster mushroom. 2010a).

Pleurotus cornucopiae Two different ACE inhibitors (oligopeptides) from Pleurotus cornucopiae have been identified with IC50 values of 0. cornucopiae fruiting body also showed a clear antihypertensive effect on spontaneously hypertensive rats at a dosage of 600 mg/kg (Jang et al.7 cells. 2006b).26 Da. and the secretion of osteoprotegerin from the osteoblasts showed marked increases after treatment with PEX. but inhibited lipopolysaccharide (1 g/mL)induced expression. Pleurotus eryngii The effects of Pleurotus eryngii extracts (PEX) on bone metabolism have been studied. The results showed that PCP-3A failed to affect RAW 264.42.46 and 1. including iNOS and NF-kappaB (Chen et al.. eryngii.studied in Raw 264.. The amino acid sequences of the two purified oligopeptides were RLPSEFDLSAFLRA and RLSGQTIEVTSEYLFRH. 2011a). The ergothioneine content of mushrooms has been reported to be in the range of 0. bisporus studied.7 viability at a concentration up to 6. PEX treatment showed an increase in the alkaline phosphatase activity of osteoblasts and in the osteocalcin mRNA expression from primary osteoblasts. and the production of NO and PGE2 in lipopolysaccharide-activated macrophages via the down-regulation of certain pro-inflammatory mediators. using rats with ovariectomy-induced osteoporosis revealed that PEX alleviated the decrease in the trabecular bone mineral density (Kim et al. Water extracts of the P. 2011a). Pleurotus ostreatus.14 mg/ml. P. The molecular mass of the purified ACE inhibitors was estimated to be 1622.0mg/g (dry weight). respectively. The white Agaricus bisporus contained the least ergothioneine and portabellas (brown) contained the highest within the varieties of A.. In vivo studies. Grifola frondosa) all contained a statistically significant greater amount of ergothioneine 230 . The specialty mushrooms tested (Lentinus edodes.85 and 2037. PEX also increased the expression of the Runx2 gene.25 g/mL.

COX-1 and -2 (Diyabalanage et al. 2006). Ceramide from Agrocybe aegerita has also been reported to inhibit the cyclooxygenase enzymes. Hypersensitivity pneumonitis induced by Pleurotus eryngii spores has been reported in a worker in an Eringi (Pleurotus eryngii) mushroom factory who had worked there for 6 years. more than 30 cases of HP induced by mushroom spores have been reported and therefore this is an 231 . and transbronchial lung biopsy specimens showed lymphocyte alveolitis with epithelioid cell granulomas in the alveolar spaces. except for the extract of Lentinula edodes (Fui et al. In Japan. The diagnosis was hypersensitivity pneumonitis (HP) caused by Eringi spores. however. In a thermal oxidative stability test. the ethyl acetate extracts of Ganoderma applanata. The antioxidative potency of commercially available mushrooms in Taiwan has been studied. Chest radiography showed diffuse fine nodular shadows. After admission. Naematoloma sublateritium. and P. bisporus. The lymphocyte count in the bronchoalveolar lavage fluid was increased. The patient suffered from hypoxemia while breathing room air. The order of inhibitory activity of mushroom extracts on oxidation in emulsion system was Agaricus bisporus > Hypsizigus marmoreus > Volvariella volvacea > Flammulina velutipes > Pleurotus eryngii > Pleurotus ostreatus > Hericium erinaceus > Lentinula edodes.compared to A. Of the mushrooms tested. 70% ethanolic extracts showed lower inhibitory activity against both enzymes compared to ethyl acetate extracts. Pleurotus eryngii.. 2008). The lymphocyte stimulating test was positive against extracts of Eringi spores.. no significant difference was found between the specialty mushrooms (Dubost et al. Of the culture media tested in this study. on his return to work.. 2008). fever and hypoxemia appeared again. In general. using lard. However. only the ethyl acetate extracts of the culture medium of Agrocybe cylindracea exhibited high inhibition of the COX-2 enzyme (Elgorashi et al. 2002). salmoneostramineus showed the highest COX-2 inhibitory effects compared to COX-1 inhibition. the patient's symptoms improved rapidly without medication. Precipitins against the extracts of Eringi spores were detected by the double immunodiffusion test. the order of antioxidative activity of the mushroom extracts showed similar tendencies. Chest computed tomography demonstrated centrilobular nodules and increased attenuation in both lungs. Mycelial extracts (ethyl acetate and 70% ethanol) of 20 higher Basidiomycetes edible or medicinal mushrooms and culture media extracts (ethyl acetate and Butan-1-ol) have been evaluated for in vitro anti-inflammatory activity using the cyclooxygenase-1 and -2 enzymes (COX-1 and -2)..

Furthermore.and methanol-extracts from the fruiting bodies of Pleurotus eryngii (Alam et al. PKC. Ubiquinone-9-induced cell death was characterised with the cleavage of poly (ADP-ribose) polymerase and pro-caspase 3. determined by beta-carotene-linoleic acid. including release of hexosaminidase and histamine. Histopathological observations indicated that the extract could effectively prevent excessive lipid formation in liver tissue (Chen et al. 2009).. A water-soluble polysaccharide extract of Pleurotus eryngii has been shown to significantly increase the activitiy of antioxidant enzymes and effectively remove free radicals in a liver-injury mouse model. in antigen-sensitized RBL-2H3 cells. Antioxidant activity. DPPH.. 2011a). 2011). and MAP kinases. 2011). 232 . and increased high-density lipoprotein cholesterol. Apoptotic cell death of human leukaemia U937 cells by ubiquinone-9 purified from Pleurotus eryngii has been reported (Bae et al. 2012b). 2003). in a high-fat-load mouse model.occupational health and safety issue. the extract decreased total cholesterol. acetone. PLCgamma2.. Akt.. total triglyceride. The data indicate that this extract from P. The symptoms appear to improve without medication (Miyazaki et al..42 mg/ml) (Oke and Aslim. ferrous-ion chelating abilities. PEE also decreased the levels of proinflammatory cytokines and COX-2 and iNOS expression in antigen-sensitized mast cells. The anti-allergenic potential of Pleurotus eryngii extract (PEE) in antigen-stimulated RBL2H3 mast cells has been evaluated with PEE inhibiting allergy markers. and suppressed antigen-induced signal protein phosphorylation of Lyn. PEE also suppressed the expression and production of interleukin-4 and reduced antigen-induced NFAT and NF-kappaB transcriptional activity in antigen-sensitized mast cells. Pleurotus eryngii and Auricularia auricula-judae both exhibit a protective effect against H2O2 induced oxidative cell damage with a P. eryngii methanolic extract also possessing the higher ferrous iron chelating ability (IC50 = 0. reducing power. eryngii may provide some insights into the mechanisms for the possible prevention and treatment of allergic and inflammatory responses (Eun Hee et al. and xanthine oxidase inhibitory activity have been demonstrated in aqueous-. related to air quality in mushroom factories that needs to be addressed. and low-density lipoprotein cholesterol.

Intake of Pleurotus eryngii also significantly reduced the homeostasis model measurement of insulin resistance.. the ethanol extracts showed strong cytotoxicity against A549 cells at concentrations over 10 µg/mL and against SiHa and HeLa cells at concentrations over 40 µg/mL. total cholesterol and triglyceride. 2010). Kim et al.. 233 . A study using isolated goat eye lens has reported that an extract of Pleurotus florida was able to prevent glucose-induced cataract in this in vitro model system (Aditya et al. SiHa and HeLa cells were incubated with different concentrations of ethanol and hot water extracts. 2010d). When A549. and increased high density lipoprotein (HDL)-cholesterol levels demonstrating hypoglycaemic and hypolipidemic effects and an improvement in insulin sensitivity in this mouse model (Jung-In et al.. 2011). A hypolipidemic effect of Pleurotus eryngii extract has also been shown in fat-loaded mice and suggested to be due to low absorption of fat caused by the inhibition of pancreatic lipase (Mizutani et al.. Pleurotus florida Anti-tumour potential of the medicinal mushroom Pleurotus florida against T24 bladder cancer cell lines has been demonstrated (Selvi et al.Intake of Pleurotus eryngii (5% supplementation with a normal diet) has been shown to decrease plasma glycated haemoglobin and serum glucose levels in a diabetic (db/db) mouse model.. 2011). Pleurotus ferulae Ethanol and hot water extracts of Pleurotus ferulae have been shown to have anti-tumourigenic properties in human cervical cancer and human lung cancer cell lines. 2010.. The ethanol extracts were the most prominent anti-tumour agents (of those studied) toward A549 human lung cancer cells (Choi et al. 2004a).

respectively. or enzyme profiles.06%.2 U/mL) significantly. phospholipids and LDL/HDL ratio by 31.47 mmol/L. The data suggest that P. triglyceride.01. chloride. 31. 11 female. nebrodensis was acting on the atherogenic lipid profile in these hypercholesterolemic rats (Alam et al. Pleurotus ostreatus (Oyster Mushrooms) A human intervention study has evaluated the cholesterol lowering properties of an Oyster mushroom (Pleurotus ostreatus) diet. 62. creatinin. Pleurotus ostreatus at the concentration taken in this study did not lower non-HDL cholesterol in HIV 234 . total bilirubin..65 and 53. and showed a significant tendency in lowering total cholesterol values (0. Twenty subjects (9 male. A single-arm.059). uric acid. glucose. potassium. magnesium. No adverse effects were reported on plasma albumin. total lipid. direct bilirubin. open-label. The feeding of these mushrooms increased total lipid and cholesterol excretion in feces.Pleurotus nebrodensis Feeding hypercholesterolemic Sprague-Dawley albino rats a diet containing 5% fruiting bodies of Pleurotus nebrodensis reduced plasma total cholesterol.. 20-34 years) were randomized to take either one portion of soup containing 30 g dried oyster mushrooms or a tomato soup as a placebo daily for 21 days.50. low-density lipoprotein. 2011c). sodium. blood urea nitrogen. 24. Essentially identical results were also reported for Pleurotus ferulae in the same animal model (Alam et al. No effects on low density lipoprotein and high density lipoprotein levels were observed (Schneider et al. proof-of-concept study of 8 weeks duration has been completed which assessed the safety and efficacy of Pleurotus ostreatus (15 g/day orally) in HIVinfected individuals taking antiretroviral therapy that induced hyperlipidemia. with significant reductions in body weight.. p = 0.91.44 mmol/L) and oxidized low density lipoprotein levels (7. 47. 2011). total protein.71. The Oyster mushroom soup decreased triacylglycerol concentrations (0. 2011b). calcium. inorganic phosphate.

once per day for 2 months. total cholesterol and triglycerides significantly.patients with antiretroviral treatment-induced hypercholesterolemia. There were no deleterious effects on liver or kidney function (Khatun et al. These results indicate that insoluble beta-glucan supplementation from P. The effect of Oyster mushrooms on reduction of blood glucose.. placebo-controlled study has investigated the effect of pleuran. 2007). the athletes underwent a 20 min intensive exercise session. A double blind. 20 elite athletes were randomized to betaglucan (n=9) or placebo ( n=11). In addition.. Mushroom consumption significantly reduced systolic and diastolic blood pressure.3/1.6) glucan from mushroom Pleurotus ostreatus. 2011). Fifty athletes were randomized to pleuran or placebo. These findings indicate that pleuran may serve as an effective nutritional supplement for athletes under heavy physical training. Incidence of URTI symptoms together with characterization of changes in phagocytosis and natural killer (NK) cell count was monitored. the phagocytosis process remained stable in pleuran group during the study in contrast to placebo group where significant reduction of phagocytosis was observed. A 28% reduction in natural killer (NK) cell activity below baseline was observed in the placebo group during the recovery period (1 h after exercise)... 2011). lowered plasma glucose.P leuran significantly reduced the incidence of URTI symptoms and increased the number of circulating NK cells. 2010). cholesterol and triglycerides in diabetic patients has been evaluated in a clinical investigation of 89 subjects. whereas no significant reduction in NK cell activity was found in the beta-glucan group. 235 . ostreatus may play a role in modulating exercise-induced changes in NK cell activity in intensively training athletes (Bobovcak et al. Immune cell counts did not differ significantly between the groups. Small changes in HDL and triglycerides were not of a clinical magnitude to warrant further study (Abrams et al. respectively. The mechanisms of pleuran function are yet to be determined (Bergendiova et al. these groups consumed 100 mg of beta-glucan (Imunoglukan) or placebo supplements. whereas there was no significant change in body weight. taking pleuran or placebo supplements during 3 months. and no significant decrease in NK cell count was measured in the beta-glucan group during the recovery period. At the end of the supplementation period. In a similar double-blind pilot study. Prolonged and exhausting physical activity causes numerous changes in immunity and sometimes transient increases the risk of upper respiratory tract infections (URTIs). an insoluble beta-(1. on selected cellular immune responses and incidence of URTI symptoms in athletes.

The content of cholesterol in high-density lipoproteins (HDL) was not influenced by the mushroom. The study concluded that 5% P. The decrease in serum cholesterol level was a consequence of the decreased cholesterol concentration in very-low-density lipoproteins (VLDL) and in low-density lipoproteins (LDL). 2003). 1999). non-esterified fatty acid by ~30% and total liver cholesterol levels by > 34%. 236 . concomitant with a decrease in plasma total cholesterol.. 1993a). these effects were not observed in mushroom-fed normocholesterolaemic rats. but was significantly reduced by 13% in liver.. A similar hypocholesterolemic effect of the oyster mushroom (Pleurotus ostreatus) was also observed in hamsters (Bobek et al.and hypercholesterolaemic rats. 1993b) and in rabbits (Bobek and Galbavy. Dietary Pleurotus ostreatus increased the fractional turnover rate of LDL (by 28%) and HDL (by 31%) as determined by the analysis of decay curves of 125I-labelled lipoproteins. Similar results have been observed in rats with a hereditary hypersensitivity to dietary cholesterol (Bobek et al.. with a concurrent increase in plasma high-density lipoprotein-cholesterol concentration of > 21%... 1990).A hypo-cholesterolemic effect has been shown with Oyster mushrooms (Pleurotus Ostreatus) in rats with Streptozotocin-induced diabetes. The addition of 4% dried whole oyster mushroom (Pleurotus Ostreatus) to the diet of Wistar rats has been reported to have led to a reduced level of serum and liver cholesterol at the end of the 10th week of the experiment. The hypo-cholesterolemic effects of Oyster mushrooms has been demonstrated to be dose-dependent (Bobek et al. while plasma total antioxidant status was significantly decreased in mushroom-fed hypercholesterolaemic rats. The increase in the rate of LDL and HDL catabolism is one of the mechanisms which mediates the hypocholesterolemic effect of mushrooms in the rat model (Bobek et al. The level of serum triacylglycerols was not influenced by the mushroom. by acting on the atherogenic lipid profile in the hyper-cholesterolaemic condition (Hossain et al. 1997). However. at least partially. triglyceride by ~34%. ostreatus supplementation provides health benefits. Feeding of 5% powder of the fruiting bodies of the Oyster mushroom (Pleurotus ostreatus) to hyper-cholesterolaemic rats reduced their plasma total cholesterol by ~28%. 1991). Oyster mushroom (4% dry oyster mushroom fruit body) lowered cholesterol content by more than 60% in the liver although it did not significantly affect either the serum triacylglycerol level or the content in liver (Bobek et al. lowdensity lipoprotein-cholesterol by ~55%.. Mushroom feeding significantly increased plasma fatty acid unsaturation in both normo.

In vivo injection of three water-soluble proteoglycan fractions from Pleurotus ostreatus mycelia. Colitis was induced by intraluminal instillation of 4% acetic acid and after 48h the extent of colonic damage and several biochemical parameters were examined.The effects of pleuran. 2006). 2010).. Pleuran was given either as a 2% food component or as a 0. A hot-water-soluble fraction of the mycelium of the liquid cultured mushroom was partially isolated and chemically characterized as a low-molecular-weight alpha-glucan. and demonstrated its direct effect on colon cancer cell proliferation via induction of apoptosis . 2011a). The mechanism of the described protective effect of pleuran is not yet clear.3 respectively. 2006). 237 . but the authors suggest that the pleuran-enhanced antioxidant defence of the colonic wall against the inflammatory attack maybe a factor (Bobek et al. into Sarcoma-180-bearing mice decreased the number of tumour cells and cell cycle analysis showed that most of the cells were found to be arrested in pre-G(0)/G(1) phase of the cell cycle.5-b]pyridine (PhIP) and promoted by dextran sodium sulfate (DSS).programmed cell death (Lavi et al. The enhanced activity of myeloperoxidase in the inflamed colonic segment was reduced by pleuran diets. 2001). This low-molecular-weight alpha-glucan possessed anti-tumourigenic properties. ostreatus may prevent inflammation-associated colon carcinogenesis induced by 2-amino-1methyl-6-phenylimidazo[4.. All of the three proteoglycans elevated mouse natural killer (NK) cell cytotoxicity and stimulated macrophages to produce nitric oxide. Fourier transform infra red (FTIR) spectra suggested the presence of a beta-glycosidic bond in all the fractions (Sarangi et al. via combined modulatory mechanisms of inflammation and tumor growth via suppression of COX-2. which had polysaccharide to protein ratios 14.4 and 18.. a beta-glucan isolated from Pleurotus ostreatus. However..44% pleuran hydrogel drink over 4 weeks. F4/80. incidence of colon tumors and high grade dysplasia was reduced by 50 and 63% only in the 500 mg/kg dose (Jedinak et al.. have been studied in a model of acute colitis in rats. A further study by the same group also showed that the anti-inflammatory activity of Pleurotus ostreatus is mediated through the inhibition of NF-kappaB and AP-1 signaling (Jedinak et al. Ki-67 and cyclin D1 expression in mice. Pleuran supplementation both in food and in drinking fluid significantly decreased the disposition to colitis.2. 26. Anti-proliferative and pro-apoptotic activities of fractions of Pleurotus ostreatus have been evaluated in HT-29 colon cancer cells in vitro. Treatment of mice with Pleurotus ostreatus at 100 and 500 mg/kg has suggested that P. reflecting decreased neutrophil infiltration.

thereby potentially protecting against the occurrence of age-associated disorders that involve free radicals (Jayakumar et al. The results suggest that this extract of P.000mg/kg to separate groups of mice (normal and alloxan-treated mice).A dimeric lectin isolated from fresh fruiting bodies of Pleurotus ostreatus has been shown to possess potent anti-tumour activity in mice bearing sarcoma S-180 and hepatoma H22. has been shown to increase gene expression of the antioxidant enzyme catalase and reduce the incidence of free radical-induced protein oxidation during aging in rats. chromosome aberrations) and sperm abnormalities in streptozotocin-induced diabetic rats (Ghaly et al. 2011).ostreatus to aged rats resulted in a significant increase in the levels of reduced glutathione (GSH) and elevated activities of glutathione S-transferase (GST). Selenium in selenium-enriched Pleurotus ostreatus has been shown to be highly bioavailable in a study in Wistar rats (da Silva et al. 2000).. kidney. Survival in these mice was prolonged and body weight increase reduced after lectin treatment (Wang et al. 500. Treatment with mushroom Pleurotus ostreatus extract has been suggested to reduce high blood glucose level. and brain tissues of rats. An extract of Pleurotus ostreatus (200 mg/kg body weight). and serum glucose and body weight 238 .. 2010a). heart. 2010a).. Pleurotus pulmonarius extract was administrated orally at doses of 250.. A further study by the same group also showed that administration of an extract of P.. Pleurotus pulmonarius Hypoglycaemic activity of an aqueous extract of Pleurotus pulmonarius in alloxan-induced diabetic mice has been reported. glutathione reductase (GR). 2010b). genetic alterations (DNA fragmentation. The in-vitro and in-vivo antioxidant effects of the oyster mushroom Pleurotus ostreatus have recently been reviewed (Jayakumar et al. and glucose 6-phosphate dehydrogenase (G6PDH) in liver. 2011).. ostreatus can prevent the oxidation of GSH and protect its related enzymes during aging (Jayakumar et al. and 1.

Podaxis pistillaris Anti-bacterial components of the mushroom Podaxis pistillaris have recently been reported. The treatments significantly lowered the expression of proliferating cell nuclear antigen and increased the number of cells undergoing apoptosis in the colon as well as inhibiting the expression of the proinflammatory cytokine TNF-alpha in colonic tissue. Orally administered glucans from Pleurotus pulmonarius have also been recently reported to reduce acute inflammation in dextran sulfate sodium-induced experimental colitis in mice (Lavi et al. Podaxis pistillaris (Podaxales. Micrococcus flavus. Proteus mirabilis. Basidiomycetes) was found to exhibit anti-bacterial activity against Staphylococcus aureus. and on an oral glucosetolerance test in alloxan induced diabetic mice was studied. In the separate group of mice. Dietary administration of the fruiting body extract or mycelia extract of the edible mushroom Pleurotus pulmonarius to mice reduced the formation of aberrant crypt foci. and inhibition of inflammation (Lavi et al.. The data suggest that the extract possesses hypoglycaemic activity (Badole et al. while oral administration of extracts reduced the serum glucose level in alloxan-treated diabetic mice at all the doses tested after acute and chronic (28 days) administration. an oral glucose tolerance test was carried out. three epidithiodiketopiperazines were identified by activityguided isolation. 2011). induction of apoptosis. In a culture medium of P. and of microadenomas. The extract also showed increased glucose tolerance in both normal and diabetic mice. pistillaris. Podaxaceae.000mg/kg.were measured. Serratia marcescens and Escherichia coli. Based on spectral data their identity was established as 239 . In a subsequent study by the same group. which precedes colorectal cancer. 2007). the interaction of an aqueous extract of Pleurotus pulmonarius with acarbose on serum glucose levels. 2010).. The anti-hyperglycaemic effects of aqueous extract and acarbose alone were similar but combination treatment of the Pleurotus pulmonarius extract with acarbose produced a more synergistic antihyperglycaemic effect than either agent alone (Badole and Bodhankar.. The extracts inhibited colitisassociated colon carcinogenesis induced in mice through the modulation of cell proliferation. 2006). Acute oral toxicity data showed no mortality in the normal mice up to 5. Bacillus subtilis.

persistent cough. and inhibitory activity toward HIV-1 reverse transcriptase. commune should be considered as one of the fungi that can cause hypersensitivityrelated lung diseases (Amitani et al. commune by use of mating tests with established monokaryotic and dikaryotic strains of S.. pistillaris (Al-Fatimi et al.epicorazine A(1). commune. 1996). epicorazine B(2) and epicorazine C (3. felt-like mycelial colonies that were later identified as the monokaryotic mycelium of S. Schizophyllum Commune (Split Gills Mushroom) A case of mucoid impaction of the bronchi due to a hypersensitivity reaction to the monokaryotic mycelium of Schizophyllum commune has been reported. antibiotic F 3822). The incidence of Schizophyllum commune related effects in patients suffering from diseases of the nasal sinuses also appears to be on the increase (Buzina et al. anti-proliferative activity toward tumour cell lines. which have not previously been reported as constituents of P. commune cytosol antigen were positive. 240 .. The patient was hospitalized because of mild asthma attacks. The authors suggested that the monokaryotic mycelium of S. A lectin from the split gill mushroom Schizophyllum commune has been shown to exhibit potent mitogenic activity toward mouse splenocytes. 2005). 2003). and "gloved finger" shadows on a chest roentgenogram. Aqueous extracts of Schizophyllum commune (27. peripheral eosinophilia. 2012). Cultures of the mucous plugs and sputum samples yielded white. but did not possess any anti-fungal activity (Han et al. The results of tests for serum antibody to S..6%) showed a relatively high Antioxidant Index (% relative to quercetin) in vitro (Abdullah et al. Bronchoscopies were effective in removing the mucous plugs and relieving the patient's symptoms.. 2006)..

Tremella fuciformis (White Wood Ear, White Jelly Leaf)
Tremella fuciformis has been shown to have hypocholesterolemic properties in rats (Cheung, 1996b).

Trametes (=Coriolus) versicolor (Turkey Tail, Yunzhi)

A systematic review of human clinical trials has
concluded that numerous dietary
polysaccharides, particularly glucans, appear to
elicit diverse immunomodulatory effects in animal
tissues, including the blood, GI tract and spleen.
Glucan extracts from the Trametes versicolor
mushroom improved survival and immune
function in human randomised clinical trials of cancer patients. Glucans, arabinogalactans
and fucoidans elicited immunomodulatory effects in controlled studies of healthy adults
and patients with canker sores and seasonal allergies. This systematic review provides a
high level of evidence for these effects (Ramberg et al., 2010)
A polysaccharide isolated from the Trametes (=Coriolus) versicolor (L.: Fr.) Lloyd
(Aphyllophoromycetideae) mushroom has been shown to induce apoptosis in a human
hepatoma cancer (QGY) cell line. The polysaccharide inhibited the proliferation of QGY in
low concentrations (<20 mg/L) and the IC50 value was 4.25 mg/L. Changes that are
characteristic of apoptosis, such as a found trapezoidal belt with DNA, were observed in
the QGY cells treated with the polysaccharide. There was a significant decrease in the
expression of the cell cycle-related genes (p53, Bc1-2, and Fas) in these cells following
treatment with the polysaccharide. The results indicated that the polysaccharide may be a
potential candidate to ameliorate toxic effects when used in cancer therapy (Cai et al.,
2010).

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Polysaccharide krestin (PSK) is an extract from Trametes versicolor, that has been shown
to be a selective toll-like receptor TLR2 agonist (Lu et al., 2011a), and the activation of
dendritic cells (DC) and T cells by PSK is dependent on TLR2. Oral administration of PSK
in neu transgenic mice significantly inhibited breast cancer growth, with the antitumor
effect of PSK being dependent on both CD8(+) T cell and NK cells, but not CD4(+) T cells.
PSK did not inhibit tumor growth in TLR2(-/-) mice suggesting that the antitumor effect is
mediated by TLR2. The data indicate that PSK is a specific TLR2 agonist and has potent
antitumor effects via stimulation of both innate and adaptive immune pathways (Lu et al.,
2011b). Components of PSK have also been reported to act as ligands for TLR4 receptors
leading to induction of TNF-alpha and IL-6 inflammatory cytokines (Price et al., 2010).
PSK has also been reported to reduce toxicity of current treatments used in patients with
metastatic colorectal cancer (Shibata et al., 2011). The effects of PSK in cancer therapy
and the possible mechanism of action have recently been reviewed (Sun et al., 2012).
Polysaccharide-K (PSK), an extract of the mushroom Trametes versicolor, has been
shown to enhance docetaxel-induced prostate cancer tumor suppression, apoptosis and
antitumor responses in transgenic adenocarcinomas of mouse prostate (TRAMP)-C2bearing mice. Combining PSK with docetaxel significantly induced higher tumor
suppression than either treatment alone, including a reduction in tumor proliferation and
enhanced apoptosis. Combined PSK and docetaxel treatment led to a lower decrease in
number of white blood cells than docetaxel alone, an effect accompanied by increased
numbers of tumor-infiltrating CD4+ and CD8+ T cells. PSK with or without docetaxel
significantly enhanced mRNA expression of IFN-gamma compared to control, but did not
significantly alter T-regulatory FoxP3 mRNA expression in tumors (Wenner et al., 2012).
Yunzhi (Coriolus versicolor) has been reported to modulate various immunological
functions in vitro, in vivo, and in human clinical trials, while Danshen (Salvia miltiorrhiza)
has been shown to benefit the circulatory system by its vasodilating activity. A clinical trial
has been carried out to evaluate the immunomodulatory effects of Yunzhi-Danshen
capsules in post-treatment breast cancer patients. Eighty-two patients with breast cancer
were recruited to take Yunzhi and Danshen capsules with the data showing that the
percentage and the absolute counts of B-lymphocytes were significantly elevated in
patients with breast cancer after taking Yunzhi-Danshen capsules, while plasma sIL-2R
concentration was significantly decreased (Wong et al., 2005). The significance of these
findings is not yet clear.
A polysaccharopeptide from the Turkey Tail fungus Trametes (=Coriolus) versicolor has

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been reported to be capable of inhibiting human immunodeficiency virus type 1 (HIV-1)
reverse transcriptase and protease, the two enzymes of paramount importance to the life
cycle of the HIV. The polysaccharopeptide inhibited other proteases including trypsin,
chymotrypsin, proteinase K, subtilisin, and elastase to a lesser extent. The anti-HIV
enzyme and immuno-stimulatory activities of the mushroom polysaccharopeptide make it
an interesting potential candidate for the therapeutic treatment of AIDS (Tzi et al., 2006),
although clearly further studies are required to confirm such effects. A recent report has
also suggested that the culture (harvest) duration affects the immunomodulatory and anticancer effects of polysaccharopeptides derived from Coriolus versicolor (Lee et al., 2006).
Coriolus versicolor (CV), also known as Trametes versicolor, has been evaluated for its
cytotoxic activities on a B-cell lymphoma (Raji) and two human promyelocytic leukemia
(HL-60, NB-4) cell lines. The results demonstrated that CV extract at 50 to 800mg/ml
dose-dependently suppressed the proliferation of Raji, NB-4, and HL-60 cells by more
than 90%. The extract however did not exert any significant cytotoxic effect on the normal
liver cell line WRL when compared with a chemotherapeutic anti-cancer drug, mitomycin
C, confirming the tumour-selective cytotoxicity. Nucleosome production in HL-60, NB-4
and Raji cells was 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 apoptosisdependent pathway (Lau et al., 2004).
Coriolus versicolor polysaccharide (CVP) extracted from C. versicolor dry fruit bodies by
hot-water extraction and ethanol precipitation has been evaluated against four human liver
cancer (7703, HepG2, 7721, PLC) and four human breast cancer (Bcap37, ZR75-30,
MCF-7, T-47D) cell lines using a cytotoxicity assay. The results showed that the CVP
inhibited the proliferation of 7703, Bcap37, T-47D in low concentration and also inhibited
the proliferation of MCF-7 and ZR75-30, but at high concentrations. The CVP did 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 (Zhou et al., 2007).
The effect of dietary supplementation with a protein-bound polysaccharide (PSP)containing extract derived from mycelia of Coriolus versicolor on in vitro and in vivo
indices of immune function of young and old C57BL/6NIA mice has been studied. Young
(5 month) and old (23 month) mice were fed purified diets containing 0%, 0.1%, 0.5% or

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1.0% PSP for 1 month after which time indices of immune function were measured. PSP
supplementation had no significant effect on mitogenic response to concanavalin A (Con
A), phytohemagglutinin (PHA) or lipopolysaccharide (LPS), or on the production of
interleukin (IL)-1, IL-2, IL-4 and prostaglandin E-2 (PGE(2)). Of the in vivo indices of
immune function tested, old mice fed 1.0% PSP had significantly higher delayed-type
hypersensitivity (DTH) response than those fed 0% PSP. No significant effect of PSP was
observed on the DTH response of young mice. The antibody response to sheep red blood
cells was not significantly influenced by PSP in young or old mice, suggesting that the
PSP-containing extract from mycelia of Coriolus versicolor might have a modest immunoenhancing effect in aged mice, but not in young mice (Wu et al., 1998).
Toth et al. have reported the inhibition of intestinal cancer by a hot water extract of the
Coriolus versicolor (Turkey Tail) mushroom in C57bl/6j-Apc(Min) mice (Toth et al., 2007).
A highly N-methylated cyclic heptapeptide, isolated from the mushroom Coriolus
versicolor, has been shown to have an inhibitory effect on fat accumulation by 3T3-L1
murine adipocytes (EC50 = 0.02µg/mL) (Shimokawa et al., 2008).
The potential toxicity of Coriolus versicolor standardized water extract after acute and
subchronic administration in rats has been studied. In the acute toxicity study, Coriolus
versicolor water extract was administered by oral gavage to Sprague-Dawley (SD) rats (6
males, 6 females) at single doses of 1250, 2500 and 5000 mg/kg. In the subchronic toxicity
study, the extract was administered orally at doses of 1250, 2500 and 5000 mg/kg/day for 28
days to male and female SD rats respectively. There was no mortality or signs of toxicity in the
acute and subchronic toxicity studies under the above conditions (Hor et al., 2011).
PSP, an active component extracted from Coriolus versicolor has been reported to be
effective in targeting prostate cancer stem/progenitor cells (CSCs). Treatment of the
prostate cancer cell line PC-3 with PSP led to the down-regulation of CSC markers
(CD133 and CD44) in a time and dose-dependent manner. PSP treatment also inhibited
PC-3 cell tumorigenicity in vivo, indicating that PSP can suppress prostate CSC
properties. Transgenic mice (TgMAP) that spontaneously develop prostate tumors, that
were orally fed with PSP for 20 weeks did not develop tomours, while 100% of the mice
that were fed with water only developed prostate tumors at the end of the 20 weeks,
suggesting that PSP treatment can inhibit prostate tumor formation in these mice (Luk et
al., 2011).

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Volvariella volvacea (Straw Mushroom)
Methanol and water extracts from Volvariella volvacea have
been shown to have antioxidant activity against lipid
peroxidation of rat brain homogenate. The ethyl acetate
sub-fraction of the methanol extract of V. volvacea was
found to have comparable antioxidant activity to caffeic acid
against the oxidation of human low-density lipoprotein
(LDL). The antioxidant activities against lipid peroxidation
were found to correlate with the phenolic content in different
sub-fractions of the mushroom extracts (Cheung and Cheung, 2005).
A report on the fractionation of extracts of the edible mushroom, Volvariella volvacea, has
shown the isolation of two heterocyclic carboxylic acids, namely pyridine-3-carboxylic acid
[nicotinic acid] and pyrazole-3(5)-carboxylic acid and four steroidal metabolites ergosterol,
5-dihydroergosterol, ergosterol peroxide, and cerevisterol. In light of the structural
similarity of pyrazole-3(5)-carboxylic acid to pyrazole-3-carboxylic acids, which act as
agonists for nicotinic acid receptors, the levels of pyridine-3-carboxylic acid and pyrazole3(5)-carboxylic acid were estimated in V. volvacea and two other edible mushrooms,
namely Agaricus bisporus and Calocybe indica. Significant levels of pyridine-3-carboxylic
acid (nicotinic acid) were found in C. indica, and pyrazole-3(5)-carboxylic acid was found
in abundance in A. bisporus. Correlations have been suggested between the occurrence
of these compounds in mushrooms and consumption as well as beneficial health effects
(Mallavadhani et al., 2006).
Volvariella volvacea has been reported to produce a hypotensive response in animals. An
aqueous extract of the mushroom (SME) was prepared and given through intravenous
injections to normotensive rats. An i.v. injection of SME produced a hypotensive effect in
rats with an ED50 of 25mg dry weight/kg body weight. SME did not increase urinary
excretion or sodium diuresis. It produced positive chronotropic and inotropic effects on
isolated right atria and induced contraction of isolated tail artery strips. This latter
contractile response was inhibited by antagonists of serotonin and alpha-adrenoceptor,
ketanserin and phentolamine respectively. Partial purification using dialysis and liquid
chromatography revealed that the hypotensive active substances had molecular weights
between 8,000 and 12,000 daltons. These substances were heat stable and resistant to
trypsin digestion (Chiu et al., 1995). Volvariella volvacea has also been shown to have
hypo-cholesterolemic properties (Cheung, 1996a, Cheung, 1998)

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Activity against the Gram-positive bacteria Staphylococcus aureus, has been
demonstrated in Volvariella volvacea strain R83, while Volvariella volvacea strain
ATCC62890 showed significantly less antimicrobial activity, but was reported to be a
source of antioxidants (da Silva et al., 2010b).

Wild Edible Fungi
While fungi are a good source of digestible proteins and
fibre, are low in fat and energy and make a useful
contribution to vitamin and mineral intake, nevertheless,
there are some safety concerns with wild fungi. Edible
species might be mistaken for poisonous ones, high heavymetal concentrations (in some regions and countries) in
wild edible fungi (WEF) are a known source of chronic
poisoning and the consumption of WEF can contribute
markedly to the radiocaesium intake of human subjects
(reported for the UK). Some regions of Europe have a
strong WEF tradition, particularly eastern Europe. Only
one-third of adults consume fungi (cultivated species and
WEF) throughout the UK; the average intake of fungi in the UK being estimated to be 0.12
kg fresh weight per capita per year. At least eighty-two species of wild fungi are recorded
as being consumed in the UK, although certain species (e.g. chanterelle (Cantharellus
cibarius), cep (Boletus edulis), Oyster mushroom (Pleurotus ostreatus)) are favoured over
others. Although wild edible fungi are not essential components in the daily diet, they have
been reported to be a nutritionally-valuable addition to the range of vegetables consumed
(de Roman et al., 2006).
In contrast to the above study, a recent analysis of a large variety (7 different families) of
wild edible mushrooms in Greece has shown high mineral contents and low contents of
heavy metals (Pb, Cd and As) suggesting that the mushroom species studied can be
consumed without a risk to health (Ouzouni et al., 2007).

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25. Conclusions
Although there have been relatively few direct intervention trials of mushroom consumption in
humans, those that have been completed to date indicate that mushrooms and their extracts
are generally well-tolerated with few, if any, side-effects. The most promising data appear to be
those indicating an inverse relationship between mushroom consumption and breast cancer
risk, although the data are generally based on food frequency questionnaires, which can be
affected by recall bias, and therefore these effects need to be confirmed via direct intervention
trials involving mushroom consumption. Although preliminary, new studies reporting protective
effects of mushrooms on beta-amyloid peptide toxicity and mild cognitive impairment (both
precursors to dementia) appear promising and warrant further research. Studies in humans
have shown an increase in the antioxidant capacity in urine and no evidence of liver, renal or
DNA toxicity, and no clinical problems with regard to blood test results, liver and renal function,
glucose and lipid metabolism, or blood pressure. Mushroom components/extracts have been
reported to have stronger health effects/benefits than whole mushrooms in the limited number
of direct human trials to date.
Mushrooms and mushroom components have been reported to have a myriad of positive
health benefits, mainly on the basis of in vitro and in vivo animal trials. However, the majority of
these effects are indirect in that they are due to a stimulation or modulation of natural cellular
immunity. Mushrooms and mushroom components exert many of their positive effects on
health via a balance of T helper cells, the induction of interferon-gamma and certain
interleukins or NO-mediated mechanisms. Many of these immunomodulating effects are due to
the polysaccharide content of mushrooms, either from beta-glucans or from polysaccharide–
protein complexes.

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26. About the authors
Dr Peter Roupas
Dr Roupas obtained his PhD from the Department of Medicine at Monash University,
Melbourne, Australia in 1988 and completed his postdoctoral research at the University of
Michigan Medical School, USA. During his 3 years at the University of Michigan, he was
awarded fellowships from the American Diabetes Association (Michigan) and the Juvenile
Diabetes Foundation International (New York). On his return to Australia, to the
Department of Clinical Biochemistry at the Royal Children’s Hospital, Melbourne, he was
awarded the 1991 Eli Lilly Diabetes Fellowship and a 4-year fellowship from the National
Health and Medical Research Council (NHMRC) of Australia. For the past 16 years, Dr
Roupas has been a Research Team Leader at CSIRO and a Project Leader of projects for
the CSIRO Food Futures Flagship, the Preventative Health Flagship, and the National
Centre of Excellence in Functional Foods relating to the scientific substantiation of health
messages for dietary guidelines and health claims for food standards / regulatory
applications. He is currently the Team Leader of the Knowledge Management team within
the Pre-Clinical and Clinical Health Substantiation group within CSIRO Food and
Nutritional Sciences. Dr Roupas has been an editorial reviewer for 8 scientific journals, an
author of 46 papers in peer-reviewed scientific journals, 30 conference papers and 7 book
chapters. Dr Roupas is also a Scientific Editor for Elsevier Science UK, a member of the
Editorial Board of the Journal of Functional Foods, and a member of the Society of
Editors. Dr Roupas is the Deputy Director of CSIRO Food and Health, and Affiliate Centre
of the Joanna Briggs Institute (JBI), an international collaboration of JBI Centres in 40
countries focussed on evidence-based healthcare and practice. Dr Roupas is also
accredited as a Systematic Scientific Reviewer by the Joanna Briggs Institute.
Associate Professor Manny Noakes
Dr Noakes is currently the Senior Research Dietitian and Research Scientist at CSIRO Food
Sciences and Nutrition where she is the Stream Leader for Diet and Lifestyle Programs. This
stream is a multidisciplinary team aimed at developing substantiated lifestyle intervention
strategies for overweight groups with obesity related morbidities. It relies on the
integration of CSIRO’s capabilities in nutrition, clinical science, physical activity,
behavioural science and nutritional genomics. Dr Noakes has managed clinical nutritional
trials for the CSIRO Clinical Research Unit since 1990 and has been involved in the
conduct of many published clinical studies to establish the health potential of diets, food
products, nutrients, supplements and pharmaceuticals. Further to this, CSIRO capabilities

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engineering and food sciences. she was awarded an Outstanding Achievement Alumni Award by Flinders University. The books’ success has sparked considerable community activity in healthy lifestyle behaviours. Dr Noakes was awarded 2 CSIRO medals for both Business Excellence and Research Excellence in 2005. Dr Noakes was actively involved in the research. food composition profiles and technological barriers to changing nutrient profiles. an international collaboration of JBI Centres in 40 countries focussed on evidence-based healthcare and practice. and contributes to peer review of papers for many nutrition journals. and Affiliate Centre of the Joanna Briggs Institute (JBI).in analytical techniques related to food composition and the limitation of food composition databases is critical in understanding the usefulness and limitations of nutrient intake assessment. Australia in 2006 in recognition of her achievements in nutritional science. assistance with scoping studies and project reports and alerting researchers and business staff 249 . As part of the Knowledge Management team within CSIRO Food and Nutritional Sciences. The books have collectively sold over 1 million copies in Australia as well as gaining international recognition with translations into 13 languages. and writing and editing. information management. Dr Noakes is the author of over 100 scientific papers. This includes developing in-depth literature searches and reviews. These skills are highly relevant to the assessment and interpretation of nutrient composition derived from dietary studies. Dr Noakes is a former Chair of the Heart Foundation's Nutrition and Metabolism Advisory Committee. Australia and has been involved in the development and oversight of several comprehensive evidence-based position papers on key nutrition issues that relate to diet and cardiovascular disease. Dr Noakes is the Director of CSIRO Food and Health. development and communication of the CSIRO Total Wellbeing Diet Books 1 and 2 which are aimed at minimising health risks through better nutrition and weight management. She has over 25 years experience in providing information services to scientists and researchers working in agriculture. In recognition of both the commercial success and the science which underpins the CSIRO Total Wellbeing Diet. including several scientific book chapters. Ms Margetts provides intensive information services in food and ingredient innovations to scientific groups. Christine Margetts Ms Margetts has qualifications in librarianship. She is also on the advisory panel for the Food Information Program Criteria Working Group which has provided an excellent framework for developing nutrition benchmarks for food categories based on knowledge of current population intakes of these foods. In addition. Dr Noakes is also accredited as a Systematic Scientific Reviewer by the Joanna Briggs Institute.

research directors. where she has organised and participated in industry days and conferences. specialising in weight management. Pennie Taylor Ms Taylor is an Accredited Practising Dietitian and the Senior Research Dietitian for the Clinical Research Unit at CSIRO Food and Nutritional Sciences. an international collaboration of JBI Centres in 40 countries focussed on evidence-based healthcare and practice. Ms Taylor is also accredited as a Systematic Scientific Reviewer by the Joanna Briggs Institute (JBI). analyse dietary data and assist in preparing scientific and commercial publications. Debra Krause Ms Krause has a Bachelor of Science degree from Deakin University. 3 years business development experience. marketing and intellectual property developments in the food industry. This includes 10 years dairy and meat research and extension experience. Ms Taylor has worked in the health and fitness industry for over 10 years and also works part-time in her own private practice. industry awareness articles. 10 years experience in confectionery research and applications.on scientific. Melbourne with over 26 years experience in food research organisations. researchers and companies to deliver outcomes of the $9. Ms Krause has held Secretariat roles for Dairy Australia's Ingredients by Design program and for CSIRO’s Innovative Foods Centre (IFC) 'Advanced processing and innovative foods program'. liaised with stakeholders from government. Ms Margetts is also accredited as a Systematic Scientific Reviewer by the Joanna Briggs Institute (JBI). weight-loss surgery and diabetes care. prepared fact sheets. She has a strong interest in dietary patterns associated with weight-loss surgery and the impact of surgery on dietary tolerance and long-term weight loss. Her role at CSIRO is to provide dietetic expertise to senior scientists to develop and deliver designer diets for clinical trials. including 5 years concurrent experience in milkfat research and extension activities. Ms Krause is currently part of the CSIRO Food and Nutritional Sciences (CFNS) Knowledge Management team. undertaking scientific literature searches and reviews for a range of projects and project proposals including the development of the Healthy Brain Book proposal as part of CSIRO’s Preventive Health Flagship. 250 . an international collaboration of JBI Centres in 40 countries focussed on evidence-based healthcare and practice. universities. an international collaboration of JBI Centres in 40 countries focussed on evidence-based healthcare and practice.8M IFC program. Ms Krause is also accredited as a Systematic Scientific Reviewer by the Joanna Briggs Institute (JBI). annual and final reports.

  Endometrial)   Unspecified  extract     Lingzi   Lentinan   Clitocinet     Anti-­‐cancer  (Gastric)   Polysaccharide  K   Lentinan  (in  adjunct  with   immuno-­‐chemotherapy)   Anti-­‐cancer   Ethanol  extract  of  whole   (Prostate)   mushroom   Anti-­‐Cancer   (Pancreatic  – advanced  solid   malignancy)   Immuno-­‐ modulation:   (Post-­‐menopausal   Breast  Cancer)   Immuno-­‐   Agaricus  blazei    Murill  Kyowa   (AbMK)   Ganoderma  lucidium   Lentinus  edodes   Leucopaxillus  giganteus   Lentinus  edodes   Ganoderma  lucidum   Unspecified  bioactive/   extract   Ganoderma  lucidum   Extract   Agaricus  bisporus   Irofulven  (cytotoxin)   Omphalotus  olearius   Note:  Not  an  edible  mushroom   Polysaccharide  extract   Grifola  frondosa   Andosan™   Agaricus  blazei  Murill    (AbM)   30 colonic  cancer  cells  via  up-­‐regulation  of  expression     of  pro-­‐apoptotic  proteins  and  down-­‐regulation  of   anti-­‐apoptotic  proteins     Increase  activity  of  natural  killer  cells     Ahn  et  al  2004   Improve  chemotherapy  side  effects  (e.   Liu  et  al  2009.   Eckhardt  et  al  2000   infusion  for  5  days  every  4  weeks  resulted  in  anti-­‐ tumor  activity.0%   Johnson  et  al  2009   .  (clinical  trial  first   registered  2008)   Daily  dose  of  10.5-­‐5.  and  intermittent  dosing  schedules   had  positive  pre-­‐clinical  anti-­‐tumor  effects  (in  vivo)   Immunologically  stimulatory  and  inhibitory   Deng  et  al  2009   measurable  effects  in  peripheral  blood  of  patients   free  of  disease  after  1st  treatment  (in  vivo)   Stimulation  of  whole  blood  ex  vivo  with  0.  appetite.  Inhibition  of  prostate   Stanley  et  al  2005   cancer-­‐dependent  angiogenesis  is  suggested  to  be   due  to  modulation  of  MAPK  and  Akt  signalling   Effect  of  4-­‐14g  of  extract    for  a  year  in  patients   NCT00779168   with  biochemically  recurrent  prostate  cancer  and   Ongoing  study   and  toxicity  of  prolonged  use.   Ren  et  al  2008   Prolong  survival.64mg/m2  as  a  5  minute  i.g.  non-­‐  node  metastasis       (  in  vivo)   Dose  extract  6mg  per  day  improve  the  total   Noguchi  et  al  2008a.  emotional  stability  &  general  weakness)   (in  vivo  undergoing  chemotherapy)   Anti-­‐proliferative  effects  via  induction  of  apoptosis     Chen  et  al  2010.  Ovarian.     human  prostate  cancer  cells.  b   International  Prostate  Symptom  Score  (IPSS)  of   men  with  lower  urinary  tract  symptoms  via  strong   5-­‐alphal-­‐reductase  inhibitory  activity  (in  vivo)   Inhibit  proliferation  and  induce  apoptosis  in  PC-­‐3   Jiang  et  al  2004b.v.   alopecia.  more  effective  in  patients  with   Oba  et  al  2009   lymph-­‐node  metastasis  vs.Anti-­‐  Cancer   (Cervical.

modulation   (Healthy  Volunteers)   (Himematsutake)  82%   Hericiums  erinaceum   (Yamabushitake)  14.  and  via  the   activation  of  Mitogen  Activated  Protein  Kinase   (MAPK)  pathways     Improve  insulin  resistance  potentially  by  the   mechanism  that  caused  an  increase  in  adiponectin   concentration  after  taking  the  extract  for  12   weeks  (in  vivo)   Significant  reduction  in  systolic  and  diastolic  blood   pressure.  In  vivo  there  was  a   significant  reduction  in  levels  of  IL-­‐1-­‐beta  (97%).9%   Immuno-­‐modulation   Alpha-­‐glucans   (Mild   hypercholesterolae mia)   Agaricus  bisporus   Immuno-­‐modulation   Glucan   (Cancer)   Immuno-­‐modulation   Various  mushroom   (variety  of  disease   bioactive(s)/  extract(s)   states)   Trametes  versicolor   Diabetes  (Type  II)    AbM  extract  (in   combination  with   metformain  and   gliclazide)   Unspecified  bioactive/   extract   Agaricus  blazei  Murill  (AbM)   Protein-­‐bound   polysaccharides  (A-­‐PBP   and  L-­‐PBP)     Unspecified  bioactive/   extract   Agaricus  blazei     Lentinus  edodes   Cardiovascular   Disease   (Biomarkers)   Brain  Health  &   Cognition   of  extract  containing  AbM  produced  a  dose-­‐ dependent  increase  in  all  cytokines  studied  from  2   to  399-­‐fold  (TNF-­‐alpha).  total  cholesterol  and   triglycerides  (in  vivo)       Weight-­‐controlling  and  hypolipidemic  effect  via  a   mechanism  involving  absorption  of  cholesterol  (in   vivo)   Increase  in  scores  on  cognitive  function  scales  in   men  and  women  diagnosed  with  mild  cognitive   Kim  et  al  2007   Hsu  et  al  2007   Khatun  et  al  2007   Kweon  et  al  2002   Mori  et  al  2009   .   TNF-­‐  alpha  (84%).   Improved  survival  and  immune  function  (in  vivo)   Ramberg  et  al  2010   Multiple  variety   Pleurotus  ostreatus  (Oyster   Mushroom)    Hericium  erinaceus   (Yamabushitake)   31 Effects  on  natural  killer  cells.  blood  glucose.7%   Grifolia  frondosa  2.  IL-­‐17  (50%)  and  IL-­‐2  (46%).   Consumption  of  fruit  juice  enriched  with  5g   Volman  et  al  2010a   glucans/  day  lowered  lipopolysaccharide-­‐induced   TNF  alpha  production  by  69%.  No  effects  on  IL-­‐ 1beta  and  IL-­‐6  and  decreased  production  of  IL-­‐12   and  IL-­‐10  was  observed  (in  vivo).   Discrepancy  in  results  associated  with  antioxidant   activity  of  AbM  in  vivo  and  limited  absorption  of   its  large  beta-­‐glucans  across  the  intestinal  mucosa   to  the  reticuloendothelial  system  and  blood.  macrophages.  T  cells   and  their  cytokine  production.  Contrarily  alpha   glucans  has  been  observed  to  stimulate  immune   response  in  an  in  vitro  mouse  model.

  endoplasmic  reticulum  (ER)  stress  and  oxidative   stress     Improves  the  Functional  Independence  Measure   (FIM)  score  or  retard  disease  progression  in   patients  with  dementia  (in  vivo)       Induce  synthesis  of  nerve  growth  factor  (NGF)  (in   vitro  and  in  vivo)       Agarius  blazei  Murill    (AbM)   Ganopoly®   Ganoderma  lucidum   1.   Erinacines  A  to  I   Hericium  erinacium   impairment  (in  vivo)       Protect  against  neuronal  cell  death  caused  by   beta-­‐amyloid  peptide  (A  beta)  toxicity.  anti-­‐viral  and  liver   protective  effects  in  chronic  hepatitis  B  (in  vivo).  clinical  proof  is  lacking.     To  be  noted:  authors  indicated  despite   pharmacological  activities. Farnesyl   Ganoderma  colossum   hydroquinone. Ganomycin  B   Polysaccharides   Unspecified  bioactive     extract     Agarius  brasiliensis  (previously   Agarius  blazei  ss  Heinem)   Cordyceps  (unspecified  variety)   32 Decrease  levels  aspartate  aminotransferase  and   alanine  aminotransferase.     To  be  noted:  results  based  on  a  sample  of  4   patients  thus  larger  and  controlled  studies  are   required  to  confirm  the  effects.  hence  normalising  liver   function  of  patients  with  Hepatitis  B  (in  vivo).     Hypoglycaemic  activity.   ganomycin  I     2.  Alleviate   chronic  allergic  inflammation  by  increasing  the   .   Competitive  inhibition  of  the  HIV-­‐1  protease   enzyme  by  ganomycin  B  and  docking  with  the  HIV-­‐ 1  protease  crystal  structure  by  both  compounds   Kawagishi  and  Zhuang   2008   Kawagishi  and  Zhuang   2008   Hsu  et  al  2008a   Zhou  et  al  2005   El  Dine  et  al  2009   Anti-­‐viral  activity  when  added  during  poliovirus   Faccin  et  al  2007   infection:  potentially  acting  at  the  initial  stage  of   viral  replication     Inhibit  proliferation  and  differentiation  of  Th2  cells   Sun  et  al  2010   &  reduce  the  expression  of  cytokines  by  down-­‐ regulating  the  expression  of  GATA-­‐3  mRNA  and   up-­‐regulating  the  expression  of  Foxp3  mRNA  in   peripheral  blood  mononuclear  cells.Hepatitis  B   Anti-­‐viral  (HIV)   Anti-­‐viral   (Poliomyelitis)   Asthma   Dilinoleoyl-­‐   phosphatidylethanolamin e  (DLPE)     Hericium  erinacium   Hericenones  C  to  H.

  (clinical  trial  first  registered  2011)   NCT01402115   Completed*   Effect  of  3mg/kg  body  weight  of  extract  given    2   times  /day  for  3months  to  patients  with   myelodysplasia  to  determine  any  improvement  in   their  neutrophil  count  and  function.   Heinemann  (Sun  mushroom)   Weight  loss  and   control   Mushrooms   Not  stated   Weight  loss   Mushrooms   Agaricus  bisporus   Antihperlipidaemia   (HIV  patients)   Oyster  mushroom   powder   Pleurotus  ostreatus   Glaucoma   Aqueous  extract   Pleurotus  tuberregium   Immune  function   Not  stated   Not  stated   Immune  function   (enhancement  of   hematopoiesis  in   myelodysplasia)     Extract   Grifola  Frondosa  (Maitake)   33 level  of  interleukin-­‐10  (in  vivo)   Fiber  supplements  using  ear  mushrooms  improve   constipation  related  symptoms  without  serious   side  effects  (in  vivo)       Kim  et  al  2004       Effect  of  150mg/day  for  12  weeks  of  Polycan  on   biochemical  markers  of  bone  metabolism  (clinical   trial  first  registered  2011))   Effect  on    nutritional  status  and  liver  function  of   10g/day  for  5  months  on  hepatitis  C  patients   (clinical  trial  first  registered  2007)   Substituting  mushrooms  for  meat  to  control  body   weight  in  a  caloric  restricted  diet    to  result  in  a   20lb  weight  loss  over  6  months(clinical  trial  first   registered  2008)   Dietary  compensation  for  potential  calorie  and  fat   savings  by  substitution  of    white  button   mushrooms  for  meat  products  over  4  days  (clinical   trial  first  registered  2008)   No  effect  on  lowering  of  lipid  levels  in  HIV  patients   receiving  Antiretroviral  treatment  (ART)  regimens   which  commonly  cause  significant  lipid  elevations.Constipation   Fiber   Auricularia  (Ear  mushrooms)   Osteoporosis   Polycan.  Laboratory   studies  have  shown  that  Maitake  can  reduce  the   NCT01099917   Recruiting   NCT00564811   Completed*   NCT01177085   Completed*   NCT00198770   Completed*   Abrams  et  al  2011   NCT01017068   Status  unknown   NCT01398176   Ongoing   .  purified  β-­‐ glucan  extract   Aureobasidium  pullulans   Nutritional  status  of   Hepatitis  C  patients   Dehydrated  powder   Agaricus  Blazei  (Murrill)  ss.   Effect  of  1-­‐4g/100mL  treatment  dose  on   intraocular  pressure  of  the  eye  (clinical  trial  first   registered  2009)   Effect  of  consumption  of  3oz  or  6oz  of  mushrooms   per  day  in  the  form  of  a  dietary  supplement    is   effective  in  enhancing  the  function  of  γδ  T  cells.

 MIP-­‐ 1beta  (30%).  MCP-­‐1  (22%).  IL-­‐6  (44%).growth  of  cancer  in  animals  through  enhancement   of  immune  function.  IL-­‐8  (18%).  biochemical  and  genetical  improvement  in   their  disease.  (clinical  trial  first   registered  2011)     *No  results  reported  as  of  15  June  2012 34 .  IL-­‐17  (17%)   and  G-­‐CSF  (14%).  (clinical  trial  first  registered  2011)   Agaricus  blazei  Murill   Agaricus  blazei  Murill   After  12  days'  ingestion  of  AndoSan.  G-­‐CSF  (29%).   Ingestion  of  an  AbM-­‐based  medicinal  mushroom   by  patients  with  IBD  resulted  in  interesting  anti-­‐ inflammatory  effects  as  demonstrated  by  declined   levels  of  pathogenic  cytokines  in  blood  and   calprotectin  in  faeces.     Agaricus  blazei  Murill   Effect  of  60mL  extract  daily  as  a  supplementary   NCT00970021   treatment  in  addition  to  chemotherapy  in  patients   Recruiting   with  multiple  myeloma.  IL-­‐1beta   (41%).  Faecal   calprotectin  was  reduced  in  the  UC  group.  There  were  corresponding   reductions  in  Crohn’s  disease:  IL-­‐2  (100%).  MCP-­‐1  (18%)  and   GM-­‐CSF  (17%).  to  experience   clinical.  IL-­‐17   (55%)  and  IL-­‐8  (29%)  and  for  IL-­‐1beta  (35%).  baseline   Forland  et  al  2011   plasma  cytokine  levels  in  ulcerative  colitis  was   reduced  for  MCP-­‐1  (40%)  and  in  LPS-­‐stimulated   blood  for  MIP-­‐1beta  (78%).  respectively.  Baseline   concentrations  for  the  17  cytokines  in  the  UC  and   CD  patient  groups  were  largely  similar.  IL-­‐8  (30%).  (clinical  trial  first  registered   2010)   Inflammatory  bowel   disease   (anti-­‐inflammatory)   Andosan™   Inflammatory  bowel   Andosan™   disease   (antit-­‐inflammatory)   Immuno-­‐modulation   Extract   (Multiple  myeloma)   Effect  of  daily  oral  ingestion  of  30mL  x2  for  21   NCT01496053   days    AndoSanTM  in  patients  with  ulcerative  colitis   Recruiting   (UC)  and  Crohn`s  disease  (CD).

 U937.  Lau   et  al  2004   Weng  et  al  2007.   Lin  et  al  2003   Barbisan  et  al  2002.   Calvino  et  al  2010.g.HL60.  MOLT4. Unspecified   bioactive/  extract(s)   Unspecified  bioactive/   extract(s)   Ganoderma  lucidum     Pleurotus  tuberregium     Cordyceps  sinensis  and   Inonotus  obliquus   Inhibit  proliferation  of  HepG2  human   hepatocellular  carcinomas     Exhibit  tumor-­‐selective  cytotoxicity  (in  vitro)   Agaricus  blazei   Pleurotus  pulmonarius   Hepato-­‐protective  effects  on  both  chemically-­‐ induced  liver  toxicity  and  hepato-­‐carcinogenesis  in   rodents    (in  vivo)   Aqueous  extract   Hypsizigus  marmoreus   Intraperitoneal  administration  exhibit  inhibitory   activity  against  spontaneous  tumor  metastasis  and   decreases  number  of  metastasised  nodules  in  mice   with  Lewis  lung  carcinoma  (in  vivo)   Anti-­‐cancer  (Lung)     Lee  et  al  2009c   Endo  et  al  2010   Gao  et  al  2007.  Youn  et  al  2008.   Pinheiro  et  al  2003.  Bae  et  al  2009. Triterpenoids     Hyper-­‐branched                  beta-­‐glucan   3.  Wu  et  al   2007.Table  8:  Properties  and  mechanisms  of  bioactive  compounds  and  mushroom  extracts  evaluated  in  animal  models  or  animal  cell  lines   EFFECT/  DISEASE   BIOACTIVE  or  EXTRACT   MUSHROOM  VARIETY   MECHANISM   REFERENCE   STATE     (in  vitro/  in  vivo)   Maitake   M ushroom   D   Grifola   f rondosa   Reduce   g rowth   i n   T24  bladder  cancer  cells   Anti–cancer  (-­‐ Louie  et  al  2010   Fraction  (in  combination   potentially  by  triggering  double-­‐stranded  DNA-­‐ (Bladder)   with  interferon-­‐alpha  2b)   dependent  protein  kinase  activation  that  may  act   on  the  cell  cycle  to  cease  cancer  cell  growth  (in   vitro)   Inhibit  growth  during  cell-­‐cycle  progression  of  5637   and  T-­‐24  bladder  cancer  cells  largely  due  to  G2/M-­‐ phase  arrest  (in  vitro)   Inhibit  proliferation  of  leukemic  tumor  cell  lines   (e.     Exhibit  tumor-­‐selective  cytotoxicity  with  no   significant  cytotoxic  effects  on  normal  cell  lines  (in   vitro)   Cordycepin  (3’-­‐ deoxyadenosine)     Cordyceps  militaris   Anti-­‐cancer   (Leukemia)   Agaritine   Agaricus  blazei  Murill   Various  unspecified   bioactives/  extracts   Agaricus  bisporus.  Agaricus   blazei.   Wasonga  et  al  2008   Saitoh  et  al  1997   .  Hypsizigus  marmoreus.   Hsu  et  al  2008b.   Mizumoto  et  al  2008.   other  unspecified  varieties       Anti-­‐cancer  (Liver)   1.  Jin  et  al   2007.  Tao   et  al  2006.  K562)   Inhibit  proliferation  of  HL-­‐60  leukemia  cells  &  other   leukemia  human  cell  lines  via  induction  of   apoptosis. 2.

Lucialdehydes  A-­‐C   Ganoderma  lucidum   Unspecified  bioactive/   extract(s)   Phellinus  linteus     Anti-­‐cancer  (Lung  &   Blazein   stomach)   Anti-­‐cancer  (  Lung   and  cervical   Anti  cancer  (Skin)   DNA  damage           Agaricus  blazei  Murill   (Himematsutake)   Unspecified  bioactive/   extract(s)   Pleurotus  ferulae   Unspecified  bioactive/   extract(s)   Methanol  extract   Lentinula  edodes   Proflamin   Flammulina  velutipes     Acidic  polysaccharide   Phellinius  linteus   Unspecified  aqueous     bioactive/  extract(s)   Agaricus  blazei  Murill   Heat-­‐  labile  protein   Agaricus  bisporus   1.  Meth-­‐ A  tumor  cell  lines)  (in  vivo)   Mediate  cell-­‐cycle  arrest  at  a  low  concentration  and   apoptosis  in  response  to  a  high  dose  in  mouse  and   human  lung  cancer  cell  (in  vivo  and  in  vitro)   Induce  cell  death  and  morphological  change   indicative  of  apoptopic  chromatin  condensation  in   human  lung  cancer  LU99  and  stomach  cancer   KATOIII  cells   Exhibit  cytotoxic  effects  on  human  lung  and  cancer   cell  lines  (A549.  SiHa  and  HeLa  cells)  (  in  vitro)   Gao  et  al  2002     Reduce  cell  proliferation  and  induce  apoptosis  in   CH72  mouse  skin  carcinoma  cells  (in  vivo)   Reduce  B-­‐16  melanoma  cell  viability  and  the   proliferation  of  tumor  cells  (arrest  in  the  G-­‐/G1   phase  of  the  cell  cycle)  followed  by  apoptotic  and   secondary  necrotic  cell  death  (in  vitro)   Increase  median  survival  time  of  mice  treated  with   B-­‐16  and  Ca-­‐744  (in  vivo)   Inhibit  melanoma  cell  metastasis  in  mice   Directly  inhibit  cancer  cell  adhesion  to  and  invasion   through  the  extracellular  matrix   Increase  macrophage  NO  production  (in  vivo)   Reduce  DNA  damage  in  liver  (induced  by   diethylnitrosamine  (DEN)  in  adult  male  Wistar  rats)   (in  vivo)   Protect  Raji  cells  (human  lymphoma  cell  line)   against  H2O2O-­‐induced  oxidative  damage  to  cellular   DNA  (in  vitro)   Protective  against  H2O2O-­‐induced  oxidative  damage   to  cellular  DNA  (in  vitro)   Gu  &  Belury  2005   Guo  et  al  2007     Itoh  et  al  2008   Choi  et  al  2004   Harhaji  et  al  2008   Ikekawa  et  al  1985   Han  et  al  2006   Barbisan  et  al  2003   Shi  et  al  2002   Rocha  et  al  2002   .  Sarcoma  180. Hot  (100°)  water    Agaricus  bisporus   Ganoderma  lucidum   Coriolus  versicolour   36 Cytotoxic  against  murine  and  human  tumor  cells   (Lewis  lung  carcinoma.  T-­‐47D. Cold  (20°)  water   extracts   2.

extracts   Unspecified  bioactive/   extract(s)   Inonotus  obliquus   Reduce  DNA  fragmentation     Aqueous  extract   Agrocybe  cylindracea  (strain  B)   Beta-­‐glucan   Agaricus  brasiliensis   Beta-­‐glucan   Agaricus  blazei   3.3/1.6)-­‐D-­‐glucan     Pleurotus  ostreatus   Bone  Health   Ethanol  extracts   Vitamin  D2  and/or   calcium   Ganoderma  lucidum   Lentinula  edodes     (UV  irradiated)       Aqueous  extract   Grifola  frondosa       37 Protection  of  radiation-­‐induced  plasmid  pBR322   DNA  strand  breaks  and  inhibition  of  lipid   peroxidation     Strong  protective  effects  against  oxidative  damage   possibly  associated  with  Se’s  role  in  increasing   antioxidant  activities  of  protein  extracts   Protection  of  DNA  from  hydroxyl  radical  oxidative   damage     Immuno-­‐modulating  effect  on  all  cytokine  plasma   levels  measured  (in  vivo)   Improve  bone  density  in  rats   May  improve  bone  mineralisation  through  a  direct   effect  on  the  bone  and  by  inducing  the  expression   of  calcium  absorbing  genes  in  the  duodenum  and   kidney  (in  vivo)   Increase  alkaline  phosphatase  activity  of   osteoblasts     Increase  mineralisation  hence  acting  as  a  bone-­‐ Park  et  al  2004     Wang  et  al  2004   Angeli  et  al  2006   Angeli  et  al  2009   Kim  &  Kim  1999   Pillai  et  al  2006   Zhao  et  al  2004       Zhao  et  al  2008   Bauerova  et  al  2009   Miyamoto  et  al  2009   Lee  et  al  2009a   Saif  et  al  2007   . Water-­‐soluble   Ganoderma  lucidum   Protects  DNA  against  OH-­‐mediated  strand  breaks   damage  in  HepG2  cells   In  the  dose  range  20-­‐80  μg/ml  exhibited  significant   dose-­‐dependent  protective  effect  against  damage   induced  by  hydrogen  peroxide  and  Trp-­‐P-­‐2     Protective  against  DNA  damage  caused  by   benzo[a]pyrene  possibly  mediated  via  binding  to   benzo[a]pyrene  or  the  capture  of  free  radicals   produced  during  its  activation     Protective  against  hydroxyl  radical-­‐induced  DNA   strand  breaks     polysaccharide.   4. Hot  water  extract   Aqueous  extract   Protein  extract       Ganoderma  lucidum   Ganoderma  lucidum  (Selenium-­‐ enriched    )   Polysaccharide  extract   Anti-­‐  Arthritic   Beta-­‐(1.

 and  beta-­‐glucan  from  SC  directly   increasing  the  synthesis  of  type  I  collagen  (in  vivo)   Active  component  with  healing  efficacy  on  acetic   acid-­‐induced  ulcers  in  rats  (in  vivo)   Reduce  ulceration    when  used  in  pre-­‐treatment  in   ethanol-­‐induced  gastric  ulcers    in  rats  (in  vivo)       Increase  activities  of  serum  antioxidant  enzymes   and  decrease  levels  of  serum  mucosal  interleukin-­‐2   (IL-­‐2)  and  TNF-­‐-­‐a  in  rats  with  oral  ulceration  (in   vivo)   In  vitro:  incubation  of  extract  with  selenite-­‐ challenged  lenses  result  in  a  decrease  in  lens   opacification  by  maintaining  antioxidant   components  at  near  normal  levels     In  vivo:  extract  prevents  cataracts  in  75%  of  rats       Pleurotus  eryngii  extracts   Pleurotus  eryngii   (PEX)   Wound  Healing   Eye  Health   Ethanol  extract   Pleurotus  eryngii   Unspecified  bioactive/   extract(s)   Agaricus  bisporus   Includes  beta-­‐glucan   Sparassis  crispa  (SC)   Polysaccharide  fractions   Ganoderma  lucidum   Unspecified  bioactive/   extract(s)   Polysaccharide     Hericium  erinaceus     Unspecified  bioactive/   extract(s)   Pleurotus  ostreatus   Lentinus  edodes     38 Kim  et  al  2006   Shimizu  et  al  2006   Batterbury  et  al  2002   Kwon  et  al  2009   Gao  et  al  2004   Mahmood  et  al  2008   Yu  et  al  2009b   Isai  et  al  2009   .inducing  agent     Alleviate  the  decrease  in  trabecular  bone  mineral   density  in  ovariectomy-­‐induced  osteporosis  in  rats   (in  vivo)   Protect  against  bone  loss  caused  by  oestrogen   deficiency     Dose-­‐dependent  inhibition  of  proliferation  and   lattice  contraction  in  an  in  vitro  model  of  wound   healing  (human  ocular  firoblasts  in  monolayers  and   in  3-­‐D  collagen  lattices)   Accelerate  wound  healing  in  diabetes  mellitus  via   an  increase  in  the  migration  of  macrophages  and   fibroblasts.