Stress, emotion, and human immune function - Ann O'Leary© (1990) The author.

Abstract - This article provides a review of empirical evidence linking emotional processes (e.g. stress) to the immune function in humans. Relationships between psycho-social factors and immunity have been identified for several diseases, including cancer and autoimmune diseases; psychosocial interventions have been tested with variable results.

Download this pdf

This 20-page article is available for free download in PDF format.

Psychological Stress and the Human Immune System: A Meta-Analytic Study of 30 Years of Inquiry - Suzanne C. Segerstrom et.al.© (2004) The author.

Abstract - The present report meta-analyzes more than 300 empirical articles describing a relationship between psychological stress and parameters of the immune system in human participants. Acute stressors (lasting minutes) were associated with potentially adaptive upregulation of some parameters of natural immunity and downregulation of some functions of specific immunity. Brief naturalistic stressors (such as exams) tended to suppress cellular immunity while preserving humoral immunity.

Chronic stressors were associated with suppression of both cellular and humoral measures. Effects of event sequences varied according to the kind of event (trauma vs. loss). Subjective reports of stress generally did not associate with immune change. In some cases, physical vulnerability as a function of age or disease also increased vulnerability to immune change during stressors.

Download this pdf

This 54-page article is available for free download in PDF format.

Enhancing versus Suppressive Effects of Stress on Immune Function: Implications for Immunoprotection versus Immunopathology - Firdaus S. Dhabhar, PhD© (2008) The author.

Abstract - It is widely believed that stress suppresses immune function and increases susceptibility to infections and cancer. Paradoxically, stress is also known to exacerbate allergic, autoimmune, and inflammatory diseases. These observations suggest that stress may have bidirectional effects on immune function, being immunosuppressive in some instances and immuno-enhancing in others.

It has recently been shown that in contrast to chronic stress that suppresses or dysregulates immune function, acute stress can be immuno-enhancing. Acute stress enhances dendritic cell, neutrophil, macrophage, and lymphocyte trafficking, maturation, and function and has been shown to augment innate and adaptive immune responses. Acute stress experienced prior to novel antigen exposure enhances innate immunity and memory T-cell formation and results in a significant and long-lasting immunoenhancement. Acute stress experienced during antigen re-exposure enhances secondary/adaptive immune responses. Therefore, depending on the conditions of immune activation and the immunizing antigen, acute stress may enhance the acquisition and expression of immunoprotection or immunopathology.

In contrast, chronic stress dysregulates innate and adaptive immune responses by changing the type 1–type 2 cytokine balance and suppresses immunity by decreasing leukocyte numbers, trafficking, and function. Chronic stress also increases susceptibility to skin cancer by suppressing type 1 cytokines and protective T cells while increasing suppressor T-cell function. We have suggested that the adaptive purpose of a physiologic stress response may be to promote survival, with stress hormones and neurotransmitters serving as beacons that prepare the immune system for potential challenges (eg, wounding or infection) perceived by the brain (eg, detection of an attacker).

However, this system may exacerbate immunopathology if the enhanced immune response is directed against innocuous or self-antigens or dysregulated following prolonged activation, as seen during chronic stress. In view of the ubiquitous nature of stress and its significant effects on immunoprotection and immunopathology, it is important to further elucidate the mechanisms mediating stress-immune interactions and to meaningfully translate findings from bench to bedside.

Download this pdf

This 10-page article is available for free download in PDF format.

Polysaccharide Immunomodulators as Therapeutic Agents - ARTHUR O. TZIANABOS - Harvard Medical School, Boston, USA © (2000) The author.

Abstract - Recently, many advances have been made toward understanding host immune responses to infectious diseases. Novel cell surface and soluble signaling molecules produced by cells of the immune system have been discovered that regulate host responses to microorganisms. It is now widely appreciated that these molecules interact in a concerted fashion to maintain a balance that governs an appropriate response to infectious organisms. Investigators have focused on discovering com- pounds that positively or negatively modulate the biologic re- sponse of immune cells and enhance the host's ability to resist microbial infection. Several classes of these compounds, such as proteins, peptides, lipopolysaccharides, glycoproteins, and lipid derivatives, have all been characterized as molecules that have potent effects on the host immune system. Peptides such as cytokines and chemokines are well-known examples of such molecules. While polysaccharides have long been believed to have benign biologic properties, certain polymers have recently been shown to act as potent immunomodulating agents. This review will focus on polysaccharides that exhibit this biologic activity and their potential for clinical use.

Download this pdf

Let food be your medicine - Why Full Nutrition Is Better than Drugs - Arden Andersen, D.O., PhD. - Interview, unknown magazine © (2010) The author.

Abstract - Arden Andersen is more than a fixture at almost every Acres U.S.A. Conference. He is a medical doctor with more than a passing interest in the real medicine of Hippocrates — "Let food be your medicine." He is also a progressive agronomist. In both roles he makes the connection between health in the soil and health in plants, animals and human beings. As a consultant, he works with growers worldwide. It is hard to say whether he is more at home as a teacher, field consultant or health practitioner. Effective in all areas, his greatest impact may well be via the students he has trained to comprehend and use the information contained in this interview and in the books he has written.

Download this pdf

This 6-page article is available for free download in PDF format (152 KB)

EXTRACTION, DEVELOPMENT AND CHEMISTRY OF ANTI-CANCER COMPOUNDS FROM MEDICINAL MUSHROOMS - anon. - exerpt from book © (2009) The authors.

Abstract - The main antitumour compounds presently isolated from mushroom fruit-bodies, submerged cultural mycelial biomass or liquid culture broth have been identified as either water soluble β-D-glucans with heterosaccharide chains of xylose, mannose, galactose or uronic acid or β-D-glucan-protein complexes – proteoglycans. Methods of extraction and purification are outlined. Levels of anti-cancer activity are related to molecular weight, degree of branching and solubility in water of the respective molecules. The main medically important polysaccharide compounds to have achieved clinical relevance, viz. Lentinan, Schizophyllan, PSK and PSP, and Grifron-D are discussed.

Download this pdf

The effects of β-glucan on human immune and cancer cells - PGodfrey Chi-Fung Chan, et.al. - Journal of Hematology & Oncology 2009, 2:25 © (2009) The authors.

Abstract - on-prescriptional use of medicinal herbs among cancer patients is common around the world. The alleged anti-cancer effects of most herbal extracts are mainly based on studies derived from in vitro or in vivo animal experiments. The current information suggests that these herbal extracts exert their biological effect either through cytotoxic or immunomodulatory mechanisms. One of the active compounds responsible for the immune effects of herbal products is in the form of complex polysaccharides known as β-glucans. β-glucans are ubiquitously found in both bacterial or fungal cell walls and have been implicated in the initiation of anti-microbial immune response. Based on in vitro studies, β-glucans act on several immune receptors including Dectin-1, complement receptor (CR3) and TLR-2/6 and trigger a group of immune cells including macrophages, neutrophils, monocytes, natural killer cells and dendritic cells. As a consequence, both innate and adaptive response can be modulated by β-glucans and they can also enhance opsonic and non- opsonic phagocytosis. In animal studies, after oral administration, the specific backbone 1→3 linear β-glycosidic chain of β-glucans cannot be digested. Most β-glucans enter the proximal small intestine and some are captured by the macrophages. They are internalized and fragmented within the cells, then transported by the macrophages to the marrow and endothelial reticular system. The small β-glucans fragments are eventually released by the macrophages and taken up by other immune cells leading to various immune responses. However, β-glucans of different sizes and branching patterns may have significantly variable immune potency. Careful selection of appropriate β-glucans is essential if we wish to investigate the effects of β-glucans clinically. So far, no good quality clinical trial data is available on assessing the effectiveness of purified β-glucans among cancer patients. Future effort should direct at performing well-designed clinical trials to verify the actual clinical efficacy of β-glucans or β-glucans containing compounds.

Download this pdf

Beta-Glucans History and the present - Immunomodulatory aspects and Mechanisms of action - M. Novak et. al - Journal of Immunotoxocology, 5:47-57 © (2008) The authors.

Abstract - A comprehensive up-to-date review of beta-glucans, their chemical and biological properties and their role in immunological reactions.

Download this pdf

Betulinic Acid induced tumor killing - Franziska B. Mullauer - AMC Amsterdam et.al.; The Netherlands © (2011) The author.

Abstract - New therapies employing novel mechanisms to induce tumor cell death are needed with plants playing a crucial role as a source for potential anti-cancer compounds. One highly promising class of natural compounds are the triterpenoids with betulinic acid (BetA) as the most prominent representative. In vitro studies have identified this agent as potently effective against a wide variety of cancer cells, also those derived from therapy resistant and refractory tumors, whereas it has been found relatively non-toxic for healthy cells. In vivo preclinically applied BetA showed some remarkable anti-cancer effects and a complete absence of systemic toxicity in rodents. BetA also cooperated with other therapies to induce tumor cell death and several potent derivatives have been discovered. Its anti-tumor activity has been related to its direct effects on the mitochondria.

Contents

• Betulinic Acid, a Natural Compound with Potent Anti-Cancer Effects
• Broad In Vitro Efficacy of Plant-Derived Betulinic Acid Against Cell Lines Derived From the Most Prevalent Human Cancer Types
• Betulinic Acid Delivered in Liposomes Reduces Growth of Human Lung and Colon Cancers in Mice Without Causing Systemic Toxicity (has not been released in the public domain yet - NOT INCLUDED)
• Betulinic Acid Induces Cytochrome c Release and Apoptosis in a Bax/Bak-Independent, Permeability Transition Pore Dependent Fashion
• Mitochondrial Damage Triggered by Betulinic Acid Induces Autophagy in Tumor Cells(has not been released in the public domain yet - NOT INCLUDED)
• Betulin is a Potent Anti-Tumor Agent That is Enhanced by Cholesterol
• General Discussion and Summary
• Summary in Dutch/Nederlandse Samenvatting

Download this pdf

Betulinic Acid for Cancer Treatment and Prevention - Simone Fulda - International Journal of Molecular Sciences © (2008) The author.

Abstract - Betulinic acid is a natural product with a range of biological effects, for example potent antitumor activity. This anticancer property is linked to its ability to induce apoptotic cell death in cancer cells by triggering the mitochondrial pathway of apoptosis. In contrast to the cytotoxicity of betulinic acid against a variety of cancer types, normal cells and tissue are relatively resistant to betulinic acid, pointing to a therapeutic window. Compounds that exert a direct action on mitochondria present promising experimental cancer therapeutics, since they may trigger cell death under circumstances in which standard chemotherapeutics fail. Thus, mitochondrion-targeted agents such as betulinic acid hold great promise as a novel therapeutic strategy in the treatment of human cancers.

Download this pdf

Betulinic Acid Inhibits Prostate Cancer Growth through Inhibition of Specificity Protein Transcription Factors - Sudhakar Chintharlapalli et.al. - American Association for Cancer Research © (2007) The authors.

Abstract - Betulinic acid is a pentacyclic triterpene natural product initially identified as a melanoma-specific cytotoxic agent that exhibits low toxicity in animal models. Subsequent studies show that betulinic acid induces apoptosis and antiangiogenic responses in tumors derived from multiple tissues; however, the underlying mechanism of action is unknown. Using LNCaP prostate cancer cells as a model, we now show that betulinic acid decreases expression of vascular endothelial growth (VEGF) and the antiapoptotic protein survivin. The mecha- nism of these betulinic acid–induced antiangiogenic and proapoptotic responses in both LNCaP cells and in tumors is due to activation of selective proteasome-dependent degra- dation of the transcription factors specificity protein 1 (Sp1), Sp3, and Sp4, which regulate VEGF and survivin expression. Thus, betulinic acid acts as a novel anticancer agent through targeted degradation of Sp proteins that are highly overexpressed in tumors.

Download this pdf

Betulinic Acid and Its Derivatives: A Review on their Biological Properties - Perumal Yogeeswari and Dharmarajan Sriram - Current Medicinal Chemistry, 2005, 12, 657-666 © (2005) The authors.

Abstract - Betulinic acid is a naturally occurring pentacyclic triterpenoid and has been shown to exhibit a variety of biological activities including inhibition of human immunodeficiency virus (HIV), antibacterial, antimalarial, antiinflammatory, anthelmintic and antioxidant properties. This article reports a survey of the literature dealing with betulinic acid related biological properties that has appeared from the 1990's to the beginning of 2003. A broad range of medical and pharmaceutical disciplines are covered, including a brief introduction about discovery, phytochemical aspects, organic synthesis, anti-HIV and cytotoxic mechanisms of action. Various structural modifications carried out and their biological and pharmacokinetic profiles are also incorporated.

Download this pdf

Alternatieven voor anti-biotica - Several authors - Ministery of Agriculture and Public Health - The Netherlands © (2009) The authors.

8 essays, in Dutch unless indicated otherwise.

• Magic bullets
• Snelle diagnostiek en smal-spectrum antibiotica
• Antibacterial vaccines (eng.)
• Bacteriophages (eng.)
• Fytobiotica
• Farmacologische antimicrobiële strategieën
• Een immunologische visie
• Een veterinair perspectief

Download this pdf

Immuunmodulatie door voedsel: rol bij allergie? - H.J. Wichers - Nederlands Tijdschrift voor Allergie en Astma, The Netherlands © (2010) The author.

Samenvatting - De laatste decennia is een afname waarneembaar van infectieziekten, tezamen met een toename van immuungerelateerde ziekten, waarvan over de oorzaken en eventuele samen- hang nog slechts hypotheses bestaan. Het functioneren van het immuunsysteem is onder andere afhankelijk van dieet en voedsel. Er is een aantal voedingsproducten in de handel met claims met betrekking tot preventie van allergische reacties, zoals pro- en prebiotica en eiwithydrolysaten. Het onderzoek naar het nut en de mogelijkheden van immuunmodu- latoir voedsel met betrekking tot allergieën is volop gaande: naast probiotica wordt onder andere onderzoek verricht aan polysacchariden en bepaalde eiwitten. Al deze 'hot topics' in het onderzoek hebben gemeen dat ze microbieel van oorsprong zijn, en zowel de aangeboren als de Th1-gemedieerde afweer lijken te stimuleren. Wellicht duidt dit erop dat een immuunsysteem dat enigszins uit balans is, in zekere mate 'heropgevoed' kan worden.

Download this pdf

Voedseleiwitten en allergische reacties - Y. Vissers, H.J. Wichers en H.F.J. Savelkoul - Nederlands Tijdschrift voor Allergie en Astma, The Netherlands © (2007) The authors.

Samenvatting - In onze voeding en leefomgeving komen zeer veel verschillende eiwitten voor, waarvan sommige in staat zijn allergische sensibilisatie te veroorzaken en bij verdere blootstelling een allergische reactie kunnen geven. De eigenschappen die een eiwit tot een allergeen maken zijn echter niet bekend. Hierdoor is op voorhand de allergeniciteit van een voedseleiwit niet te voorspellen. Daarnaast bestaat er een zeer grote mate van heterogeniteit van allergenen op basis van genetische, posttranslationele en structurele verschillen. De voedselmatrix waarin allergenen zich bevinden, kan de mate van allergeniciteit moduleren. Over deze laatste eigenschap van voeding is slechts zeer weinig bekend.

Download this pdf

The Western approach to Medicinal Mushrooms - John E. Smith, Richard Sullivan - Cancer Research UK © (?) The authors.

Abstract - Extracts of medicinal mushrooms have long been an important part of Traditional Chinese Medicine. Several purified compounds from medicinal mushrooms are used extensively in the Far East as adjuncts to cancer therapy. The Western regulatory issues with respect to medicinal mushrooms are examined and safety and quality control aspects set out.

Download this pdf

Medicinal mushrooms - their therapeutic properties and current medical usage with special emphasis on cancer treatments. - John E. Smith et.al. - Cancer Research UK © (2000) The authors.

Abstract - Many of the currently available anti-cancer agents are derived form natural products, for instance paclitaxel (Taxol), and camptothecin (Hycamtin) amongst many others. In 2000 Professor Gordon McVie, Director-General of the Cancer Research Campaign (now Cancer Research UK) and Professor John Smith of University of Strathclyde met in Glasgow to discuss the role of medicinal mushrooms in the treatment of cancer. The CRC had become aware that these natural products were being used extensively in the Far East as nutriceuticals (dietary supplements) and as a source for the generation of pharmaceutical-grade medicines to treat a wide variety of diseases, including cancer. The substantial range of medicinal mushroom species from which different bioactive compounds can be derived suggested that the humble mushroom could be a source of novel anti-cancer agents. This monograph is a comprehensive overview of this subject from the technology of cultivation, extraction and chemistry of medicinal mushroom bioactive compounds to the clinical evidence that suggests an important therapeutic role in cancer, and other major diseases.

Download this monograph

Immunomodulation by dietary mushroom compounds - H.J. Wichers, H.J. Savelkoul, et.al. - Wageningen University and Research Centre, Wageningen, The Netherlands © (2004) The authors.

Abstract - Mushrooms are long used food supplements that display profound immunomodulatory activities, due to the presence of both polysaccharides (ß-D-glucans) and proteins (FIP). These compounds work either alone or in concert and both target different aspects of the immune system. While ß-glucans are considered to bind to innate receptors and activate innate cells (dendritic cells and monocytes/macrophages), immunomodulatory proteins will be taken up, processed and presented on antigen-presenting cells to CD4+ Th cells in the context of MHC class II molecules. The outcome is different and results in the activa- tion of both innate and antigen-specific adaptive immune reactivity. The combined presence in a whole extracts is therefore expected to be of more use than either active compound alone. Here we will describe some of the immunomodulatory activities present in such extracts from edible mushrooms.

Download this pdf

Medicinal mushroom modulators of molecular targets as cancer therapeutics - Solomon P. Wasser et.al. - Applied Microbiology & Biotechnology (2005) 67: 453–468 © (2005) Springer-Verlag.

Abstract - Empirical approaches to discover anticancer drugs and cancer treatments have made limited progress in the past several decades in finding a cure for cancer. The expanded knowledge of the molecular basis of tumorigenesis and metastasis, together with the inherently vast structural diversity of natural compounds found in mushrooms, provided unique opportunities for discovering new drugs that rationally target the abnormal molecular and biochemical signals leading to cancer. This review focuses on mushroom low-molecular-weight secondary metabolites targeting processes such as apoptosis, angiogenesis, metastasis, cell cycle regulation, and signal transduction cascades. Also discussed in this review are high-molecular-weight polysaccharides or polysaccharide–protein complexes from mushrooms that appear to enhance innate and cell-mediated immune responses, exhibit antitumor activities in animals and humans, and demonstrate the anticancer properties of selenium com- pounds accumulated in mushrooms.

Download this pdf

The Pharmacological Potential of Mushrooms - Ulrike Lindequist et.al. - Originally published by Oxford University Press © (2005) The authors.

Abstract - This review describes pharmacologically active compounds from mushrooms. Compounds and complex substances with antimicrobial, antiviral, antitumor, antiallergic, immunomodulating, anti-inflammatory, antiatherogenic, hypoglycemic, hepatoprotective and central activities are covered, focusing on the review of recent literature. The production of mushrooms or mushroom compounds is discussed briefly.

Download this pdf

Immunobiology of Mushrooms - Andrea T. Borchers et.al. - Society for Experimental Biology and Medicine © (2008) The authors.

Abstract - There has been enormous interest in the biologic activity of mushrooms and innumerable claims have been made that mushrooms have beneficial effects on immune function with subsequent implications for inhibition of tumor growth. The majority of these observations are anecdotal and often lack standardization. However, there remains considerable data on both in vitro and in vivo effects that reflect on the potential of mushroom compounds to influence human immunity. A number of these effects are beneficial but, unfortunately, many responses are still characterized based on phenomenology and there is more speculation than substance. With respect to tumor biology, although many neoplastic lesions are immunogenic, tumor antigens frequently are self antigens and induce tolerance and many patients with cancer exhibit suppressed immune responses, including defective antigen presentation. Therefore, if and when mushroom extracts are effective, they more likely function as a result of improved antigen presentation by dendritic cells than by a direct cytopathic effect. In this review we attempt to place these data in perspective, with a particular focus on dendritic cell populations and the ability of mushroom extracts to modulate immunity. There is, at present, no scientific basis for the use of either mushrooms or mushroom extracts in the treatment of human patients but there is significant potential for rigorous research to understand the potential of mushrooms in human disease and thence to focus on appropriate clinical trials to demonstrate effectiveness and/ or potential toxicity.

Download this pdf

Medicinal Values of Mushrooms - Shu-Ting Chang, Philip G. Miles - CRC Press, 2nd edition © (2004) The authors.

Abstract - Mushrooms have long been considered to have medicinal value. The early herbalists were more interested in the medicinal properties of mushrooms than in their basic value as a source of food. Recently, Western society has placed a great emphasis on plants, herbs, and foods as sources of these health enhancers. About 3.5 billion people worldwide, well over half of the world's population, rely on plant-based medicines and dietary supplements for their primary health care.
Recently, the products of medicinal mushrooms have demonstrated to enhance the immune system and promote the natural defense system. They are also good for patients who have received treatment with radiotherapy or chemotherapy, as they may help to reduce the side effects from such therapies.

• increasing the number of leucocytes in the blood, and enhancing the immune functions (it has been known that chemo- therapy treatment can markedly deplete the number of platelets in the blood and put patients at risk of excessive bruising, internal bleeding, brain hemorrhage, and sometimes death);
• increasing and improving appetite;
• reducing pain;
• anti-emetic properties;
• stopping hair loss;
• inducing tumor regression;
• potential antioxidant and genoprotective properties, and
• general health-improving effects.

Exactly how these products work is still a matter of conjecture, but numerous trials (both laboratory and human) have shown, again and again, that they are effective in complementing conventional medicines in fighting diseases.
People unfamiliar with the field may ask, "If those mushrooms have such beneficial effects, can chemists isolate the active com- ponent so that it can be marketed as a drug?" If the answer is "yes," the main focus is on a single active component of the mushroom, e.g., lentinan, which is close to drug standard, and on certain diseases, e.g., cancers or heart diseases only. The products are prescription drugs. If the answer is "no," then the main focus is on a group of compounds, and on people's quality of life. The products are dietary supplements and are not single active components.
The research achievements in medicinal mushrooms during the last two decades give the impression, and the confidence, that medicinal mushrooms have much to offer to the health-care system for humans in the 21st century. In cases where modern medicines may not provide a complete remedy, complementation by mushroom nutriceuticals may augment the success of the treatment. Prevention of diseases is beneficial to everyone and deserves the same attention that is given to the curing of diseases.

Download this pdf

Anti-inflammatory and Immunomodulating Properties of Fungal Metabolites - Cristina Lull et.al. - Agrotechnology and Food Innovations, Wageningen University and Research Center, The Netherlands. © (2004) The authors.

Abstract - We discuss current information on the ability of extracts and isolated metabolites from mushrooms to modulate immune responses. This can result in a more enhanced innate and acquired disease resistance. The major immunomodulating effects of these active substances derived from mushrooms include mitogenicity and activation of immune effector cells, such as lymphocytes, macrophages, and natural killer cells, resulting in the production of cytokines, including interleukins (ILs), tumor necrosis factor alpha (TNF)-alpha, and interferon gamma (INF)-gamma. In particular, the ability of selective mushroom extracts to modulate the differentiation capacity of CD4(+) T cells to mature into T(H)1 and/or T(H)2 subsets will be discussed. As a consequence these extracts will have profound effects in particular diseases, like chronic autoimmune T(H)1-mediated or allergic T(H)2-mediated diseases. Immunosuppressive effects by mushroom components have also been observed. The therapeutic effects of mushrooms, such as anticancer activity, suppression of autoimmune diseases, and allergy have been associated with their immunomodulating effects. However, further studies are needed to determine the molecular mechanisms of the immunomodulating effects of mushrooms metabolites both individually and in complex mixtures, for example, extracts.

Download this pdf

Medicinal mushrooms and pets - Steve Marsden - Lifelearn Inc. © (2004) The author.

Short leaflet about the usefulness of medicinal mushrooms when treating pets.

Download this pdf

Review of Medicinal Mushrooms Advances: Good News from Old Allies - Solomon P. Wasser - HerbalGram. 2002; 56:28-33 American Botanical Council. © (2007) The authors

Abstract - Edible and medicinal mushrooms (macrofungi) not only can convert the huge lignocellulosic biomass* waste into human food, but -- most remarkably -- can produce notable mycopharmaceuticals, myconutriceuticals and mycocosmeceuticals. Pharmaceutical substances with potent and unique health-enhancing properties were isolated recently from medicinal mushrooms and distributed worldwide. In Japan, China, Russia, and Korea, several different polysaccharide antitumor drugs have been developed from the fruiting bodies, mycelia, and culture media of various medicinal mushrooms.The Japan Cancer Association proved that A. blazei is effective against Ehrlich's ascites carcinoma, sigmoid colon cancer, ovarian cancer, breast cancer, lung cancer, and liver cancer, as well as against solid cancers.

Download this pdf

Paddenstoelen nog niet ontdekt als gezondheidsproduct - Yang Zhu - Wageningen Universiteit en Researchcentrum, The Netherlands © (2003) The author.

Abstract - Veel soorten eetbare paddestoelen bevatten behalve een hoog gehalte aan vitamines, mineralen, aminozuren en voedingsvezels vaak ook nog andere gezondheidsbevorderende stoffen. Ze kunnen daarom een bron zijn van natuurlijke stoffen die een preventieve en/of curatieve werking hebben. In het Verre Oosten is het gezondheidsbevorderende effect van paddestoelen al eeuwenlang gemeengoed. In westerse landen zijn de toepassingsmogelijkheden ervan nog vrij onbekend.

Download this pdf

Compounds from Wild Mushrooms with Antitumor Potential - Isabel C.F.R. Ferreira, et.al. - publisher unknown - Portugal © (2008) The authors.

Abstract - For thousands of years medicine and natural products have been closely linked through the use of traditional medicines and natural poisons. Mushrooms have an established history of use in traditional oriental medicine, where most medicinal mushroom prepara- tions are regarded as a tonic, that is, they have beneficial health effects without known negative side-effects and can be moderately used on a regular basis without harm. Mushrooms comprise a vast and yet largely untapped source of powerful new pharmaceutical products. In particular, and most importantly for modern medicine, they represent an unlimited source of compounds which are modulators of tumour cell growth. Furthermore, they may have potential as functional foods and sources of novel molecules. We will review the com- pounds with antitumor potential identified so far in mushrooms, including low-molecular-weight (LMW, e.g. quinones, cerebrosides, isoflavones, catechols, amines, triacylglycerols, sesquiterpenes, steroids, organic germanium and selenium) and high-molecular-weight compounds (HMW, e.g. homo and heteroglucans, glycans, glycoproteins, glycopeptides, proteoglycans, proteins and RNA-protein complexes).

Download this pdf

Anti-cancer effect of polysaccharides isolated from higher basidiomycetes mushrooms - A.S. Daba and O.U.Ezeronye - African Journal of Biotechnology Vol. 2 (12), pp. 672-678, December 2003 © (2003) The authors.

Abstract - Anti-tumor activity of mushroom fruit bodies and mycelial extracts evaluated using different cancer cell lines. These polysaccharide extracts showed potent antitumor activity against sarcoma 180, mammary adenocarcinoma 755, leukemia L-1210 and a host of other tumors. The antitumor activity was mainly due to indirect host mediated immunotherapeutic effect. These studies are still in progress in many laboratories and the role of the polysaccharides as immunopotentiators is especially under intense debate. The purpose of the present review is to summarize the available information in this area and to indicate the present status of the research.

Download this pdf

Advances in Mushroom Research in the Last Decade - Leifa Fan et.al. - Food Technol. Biotechnol. 44 (3) 303–311 (2006) © (2006) The authors.

Abstract - There has been a lot of progress in mushroom science and biotechnology in the last decade. The optimisation of PFGE separation of fungal chromosomes allowed the study of the molecular karyotype of mushrooms and the assignment of genes to chromosomes. There are 115 genes encoded from different species of mushrooms. Cross breeding continues to be the principal method, but it is accompanied by the analyses of RAPD or RFLPs methods. The genetic makers are used and introduced into commercial large hybrids via introgression breeding. The complex traits such as yield, resistance to disease and quality characteristics, and quantitative traits more than one quantitative trait locus (QTL) are found and used in practice. The transformants or transgenic mutant strains were obtained by Agrobacterium system or particle bombardment. At least 651 species representing 182 genera of hetero- and homobasidiomycetes mushrooms were researched containing anti-tumor or immuno-stimulating polysaccharides. Ergosterol in the lipid fraction was identified as one of the most active constituents. New sesquiterpenoid hydroquinones, steroids, oxalic acid, triterpenes, water-soluble lignins, sulfated polysaccharides, protein-bound polysaccharides are researched intensively as antimicrobial or antiviral agents. Many small molecular mass compounds exhibit cytotoxic activities, such as illudins, leaianafulvene, triterpenes (ganoderic acids), acetoxyscirpenediol, ergosterol peroxide, sterols. There are many other compounds or activities found in the mushrooms, such as anti-oxidative, hypoglycemic action, anti-inflammatory effect, hepato-protective compounds, psychoactive compounds and activities.

Download this pdf

Biological and Pharmacological Activity of Higher Fungi: 20-Year Retrospective Analysis - Patrick POUCHERET, et.al. - Cryptogamie, Mycologie, 2006, 27 (4): 1-24 © (2006) Adac.

Abstract - The widespread occurrence of biological activities within the fungal kingdom is now widely accepted. Since ancient times the so called mushrooms meaning Basidiomycota have been used for medicinal purpose. All major human body functions were considered to benefit from fungi intake. These positive effects include prophylactic as well as curative actions. Historically, Oriental countries first recognised mushrooms as an important source of medicines. Recently, Occidental research starts to really consider this almost untapped source of therapeutic drugs. Indeed, discovering new major medics is becoming a great challenge. The aim of the present review is to outline past and current major therapeutic interest and pharmacology of medicinal mushrooms, and their applications in human health care. Indeed, metabolites from Basidiomycota demonstrate verified pharmacological activity in major diseases such as chronic inflammation, oxidation associated pathologies, diabetes, infections (HIV, fungi, bacteria), immune system disorder and cancer.

Download this pdf

Mushrooms as a functional food mediator in preventing and ameliorating diabetes - Kamal Perera, et.al. - Functional Foods in Health and Disease 2011; 4:161-171

Abstract - Diabetes is a major health problem predisposing to markedly increased complications. Despite the numerous preventative strategies and armories of medication, the management of diabetes remains grossly unsatisfactory. Diabetes is emerging as a pandemic. Therefore it is important to identify novel nutraceuticals or drugs for curing or preventing diabetes, which have fewer side effects. The present paper reviewed scientific information on mushrooms with regards to its anti-diabetic active compounds and/or pharmacological test results, which are commonly used as functional foods and ingredients used in the traditional medical system and which have demonstrated experimental or/and clinical anti-diabetic effectiveness. These functional foods might have a big potential for the prevention or cure of diabetes more than in other plant species. However, still scientific or clinical studies are not sufficient for hypoglycemic effect for mushrooms use as ‘official’ drug. Therefore, it is proposed that a close attention be paid to carry out further research of functional mushrooms for preventive and curative measures for diabetes and its complications.

Download this pdf

Mushroom Polysaccharides: Chemistry and Antiobesity, Antidiabetes, Anticancer, and Antibiotic Properties in Cells, Rodents, and Humans - Mendel Friedman (copyright 2016)

Abstract - More than 2000 species of edible and/or medicinal mushrooms have been identified to date, many of which are widely consumed, stimulating much research on their health-promoting properties. These properties are associated with bioactive compounds produced by the mushrooms, including polysaccharides.

Although β-glucans (homopolysaccharides) are believed to be the major bioactive polysaccharides of mushrooms, other types of mushroom polysaccharides (heteropolysaccharides) also possess biological properties.

Here we survey the chemistry of such health-promoting polysaccharides and their reported antiobesity and antidiabetic properties as well as selected anticarcinogenic, antimicrobial, and antiviral effects that demonstrate their multiple health-promoting potential.

The associated antioxidative, anti-inflammatory, and immunomodulating activities in fat cells, rodents, and humans are also discussed. The mechanisms of action involve the gut microbiota, meaning the polysaccharides act as prebiotics in the digestive system.

Also covered here are the nutritional, functional food, clinical, and epidemiological studies designed to assess the health-promoting properties of polysaccharides, individually and as blended mixtures, against obesity, diabetes, cancer, and infectious diseases, and suggestions for further research. The collated information and suggested research needs might guide further studies needed for a better understanding of the health-promoting properties of mushroom polysaccharides and enhance their use to help prevent and treat human chronic diseases.

Download this pdf

Recent developments in mushrooms as anti-cancer therapeutics- a review - Seema Patel et.al. (copyright 2012)

Abstract - The last decade has witnessed the overwhelming interest of western research fraternity in pharmaceutical potential of mushrooms. The chief medicinal uses of mushrooms discovered so far are as anti-oxidant, anti-diabetic, hypocholesterolemic, anti-tumor, anti-cancer, immunomodulatory, anti-allergic, nephroprotective, and anti-microbial agents.

The mushrooms credited with success against cancer belong to the genus Phellinus, Pleurotus, Agaricus, Ganoderma, Clitocybe, Antrodia, Trametes, Cordyceps, Xerocomus, Calvatia, Schizophyllum, Flammulina, Suillus, Inonotus, Inocybe, Funlia, Lactarius, Albatrellus, Russula, and Fomes.

The anti-cancer compounds play crucial role as reactive oxygen species inducer, mitotic kinase inhibitor, anti-mitotic, angiogenesis inhibitor, topoisomerase inhibitor, leading to apoptosis, and eventually checking cancer proliferation.

The present review updates the recent findings on the pharmacologically active compounds, their anti-tumor potential, and underlying mechanism of biological action in order to raise awareness for further investigations to develop cancer therapeutics from mushrooms.

The mounting evidences from various research groups across the globe, regarding anti-tumor application of mushroom extracts unarguably make it a fast-track research area worth mass attention.

Download this pdf

The Mushroom Agaricus blazei Murill in Combination with Metformin and Gliclazide Improves Insulin Resistance in Type 2 Diabetes - A Randomized, Double-Blinded, and Placebo-Controlled Clinical Trial - CHUNG-HUA HSU, M.D., PhD, et.al. - THE JOURNAL OF ALTERNATIVE AND COMPLEMENTARY MEDICINE Volume 13, Number 1, 2007 © (2007) Mary Ann Liebert, Inc.

Abstract - Complementary and alternative medicine use in adults with type 2 diabetes is popular. Although most of the herbs and supplements appear to be safe, there is still insufficient evidence that demonstrates their definitive beneficial effects. This study was done to determine whether the supplement of Agaricus blazei Murill extract improves insulin resistance in type 2 diabetes.

Download this pdf

Effect of Agaricus blazei Murill on the Pulmonary Tissue of Animals with Streptozotocin-Induced Diabetes - Fábio Cangeri Di Naso, et.al. - Experimental Diabetes Research Volume 2010, Article ID 543926 © (2010) Hindawi Publishing Corporation

Abstract - The present study was designed to evaluate the oxidative stress as well as the therapeutic effect of Agaricus blazei Muril (A. Blazei) in rats with streptozotocin-induced diabetes. We used 25 Wistar rats, and DM was induced by injecting streptozotocin (70 mg/Kg i.p.). Agaricus blazei Muril was administered daily starting 40 days after disease onset. A. Blazei was tested as an aqueous extract for its phytochemical composition, and its antioxidant activity in vitro was also evaluated. Lipoperoxidation (LPO), and superoxide dismutase (SOD), catalase, and glutathione peroxidase activities were measured in the pulmonary tissue, as well as the presence of inducible nitric oxide synthase (iNOS), through immunohistochemistry. An anatomopathologic study was also performed. Phytochemical screening of A. Blazei detected the presence of alkaloids and saponins. The extract exhibited a significant antioxidant activity in the DPPH-scavenging and the hipoxanthine/xanthine oxidase assays. Pulmonary LPO increased in diabetic animals (0.43 ± 0.09; P < .001) as compared to the control group (0.18 ± 0.02), followed by a reduction in the A. Blazei-treated group (0.33 ± 0.04; P < .05). iNOS was found increased in the lung in diabetic rats and reduced in the A. Blazei-treated group. The pulmonary tissue in diabetic rats showed oxidative alterations related to the streptozotocin treatment. The A. Blazei treatment effectively reduced the oxidative stress and contributed to tissue recovery.

Download this pdf

Isolation of an Antitumor Compound from Agaricus blazei Murill and Its Mechanism of Action - Takaku T. et.al. - Department of Medical Biochemistry and Central Research Laboratory, School of Medicine, Ehime University, Shigenobu-cho, Onsen-gun, Ehime 791-0295, Japan © (2001) The authors.

Abstract - The Basidiomycete fungus Agaricus blazei Murill has traditionally been used as a health food for the prevention of cancer, diabetes, hyperlipidemia, arteriosclerosis and chronic hepatitis. In the present study, we examined the antitumor activities of various substances isolated from the lipid fraction of A. blazei. Tumor growth was retarded by the oral administration of the lipid fraction extracted from A. blazei with a chloroform/methanol mixture in sarcoma 180-bearing mice. The substance with the antitumor activity in the lipid fraction was isolated via silica gel column chromatography, eluted with an acetonitrile/methanol (3:2) mixture and identified as ergosterol by direct comparison of the (1)H NMR and mass spectrometry spectral data of an authentic sample. The oral administration of ergosterol to sarcoma 180-bearing mice significantly reduced tumor growth at doses of 400 and 800 mg/kg administered for 20 d without side effects, such as the decreases in body, epididymal adipose tissue, thymus, and spleen weights and leukocyte numbers induced by cancer chemotherapy drugs. Ergosterol had no cytotoxicity against tumor cells. To clarify the antitumor activity of ergosterol, we examined the effects of ergosterol on tumor-induced angiogenesis using two in vivo models. Intraperitoneal administration of ergosterol at doses of 5, 10 and 20 mg/kg for 5 consecutive d inhibited the neovascularization induced by Lewis lung carcinoma cell-packed chambers, suggesting that either ergosterol or its metabolites may be involved in the inhibition of tumor-induced neovascularization. Therefore, we further examined the inhibitory effects of ergosterol on Matrigel-induced neovascularization. Female C57BL/6 mice were subcutaneously inoculated with Matrigel containing acidic fibroblast growth factor and heparin with or without ergosterol. Ergosterol inhibited the Matrigel-induced neovascularization, suggesting that ergosterol directly inhibits Matrigel-induced neovascularization. From these results, it seems likely that the antitumor activity of ergosterol might be due to direct inhibition of angiogenesis induced by solid tumors. This is the first report of ergosterol as an antiangiogenic substance.

Download this pdf

An extract of the medicinal mushroom Agaricus blazei Murill can protect against allergy - Linda K Ellertsen, Geir Hetland - Department of Environmental Immunology, Norwegian Institute of Public Health, Oslo, Norway - Department of Immunology and Transfusion Medicine, Oslo University Hospital, Ulleval, Oslo, Norway © (2009) The authors.

Abstract - Agaricus blazei Murill (AbM) is an edible Brazilian mushroom that has been used in traditional medicine for a range of diseases. It has been shown to have anti-infection and anti-tumor properties in the mouse, which are due to induction of Th1 responses. On the other hand, IgE- mediated allergy is induced by a Th2 response. Objective: Since according to the Th1/Th2 paradigm an increased Th1 response may promote a reduced Th2 response, the aim was to examine whether AbM had anti-allergy effects. Methods: A mouse model for allergy was employed, in which the mice were immunized s.c. with the model allergen ovalbumin (OVA). Additionally, the animals were given a mushroom extract, AndoSanTM, mainly (82%) containing AbM, but also Hericium erinaceum (15%) and Grifola frondosa (3%), or PBS p.o. either a day before or 19 days after the immunization. The mice were sacrificed on day 26, and anti-OVA IgE (Th2 response) and IgG2a (Th1 response) antibodies were examined in serum and Th1, Th2 and Treg cytokines in spleen cells cultures. Results: It was found that the AndoSanTM extract both when given either before or after OVA immunization reduced the levels of anti-OVA IgE, but not IgG2a, in the mice. There was a tendency to reduced Th2 relative to Th1 cytokine levels in the AndoSanTM groups. Conclusion: This particular AbM extract may both prevent allergy development and be used as a therapeutical substance against established allergy.

Download this pdf

Antioxidant activity and anti-tumor immunity by Agaricus, Propolis and Paffia in mice - Yeun-hwa Gu - Department of Environmental Immunology, Norwegian Institute of Public Health, Oslo, Norway - Graduate School of Health Science, Suzuka University of Medical Science, Japan © (2007) The author.

Abstract - In South America, natural products with unknown drug effects are used as folk remedies and for preventive medicine. Among South American natural products, we directed our attention to Agaricus, Propolis and Paffia, which have been known as medicinal plants, and examined the mechanisms by which these substances affect antioxidant activity, anti-tumor activity and immunoresponse. Concuding, the results strongly suggest that Agaricus, Propolis and Paffia enhance original functions of macrophages and NK (Natural Killer) cells, and as a result, secondarily enhances the immune reaction and suppresses tumor growth.

Download this pdf

ImmunoModulating Activity of Agaricus Blazei in Mice and Human volunteers - Ying Liu et.al. - Tokyo University of Pharmacy and Life Science et.al, Japan © (2007) The authors.

Abstract - We performed studies on murine models and human volunteers to examine the immunoen- hancing effects of the naturally outdoor-cultivated fruit body of Agaricus brasiliensis KA21 (i.e. Agaricus blazei). Antitumor, leukocyte-enhancing, hepatopathy-alleviating and endotoxin shock-alleviating effects were found in mice. In the human study, percentage body fat, percentage visceral fat, blood cholesterol level and blood glucose level were decreased, and natural killer cell activity was increased. Taken together, the results strongly suggest that the A. brasiliensis fruit body is useful as a health-promoting food.

Download this pdf

Agaricus blazei: cultivation and mycochemical contents - András Geösel, et.al. - Corvinus University of Budapest, Hungary © (2010) The authors.

Abstract - White button mushroom, the cream type (Agaricus bisporus) and five different A. blazei (syn. A. subrufescens) cultivars were cultivated on Phase II. mushroom compost under identical conditions in the study. We compared the yields of strains and the phenol content was measured by spectrophotometer, while total antioxidant capacity of the extracts was determined by FRAP method. Our results revealed a tight correspondence between total antioxidant capacity and total phenol content of samples. We concluded that differences can be found between mushroom species, moreover between varieties in accumulation of secondary metabolites. The measured parameters differed in stipes and caps. Based on these results it is possible to select A. blazei cultivars in other point of view, underline the fact that medicinal products and pharmaceuticals prepared from this mushroom species can be very distinct.

Download this pdf

Treatment of psoriasis with Chaga - Prof. E.A. Dosychev, V.N. Bystrova - Vestnik Dermatologii i Venerologii, 1973, May; 47(5):pp.79-83 - USSR. © (1973) The authors.

Abstract - Fifty patients with psoriasis were treated in an out-patient ward by continuous administration of aqueous solutions of official preparations of Chaga fungus. As concurrent diseases, 46 patients had different chronic inflammatory diseases of the gastrointestinal tract and 4 had chronic inflammatory diseases of the otorhinolaryngological organs. Treatment and follow-up of these patients lasted from 3 months to 2 years. Complete disappearance of psoriatic eruptions was observed in 38 patients, considerable improvement in 8 patients. No therapeutic effect was achieved in only 4 patients. Simultaneously with disappearance of psoriatic eruptions manifestations of the concurrent diseases of the gastrointestinal tract were modified or disappeared completely. Less significant therapeutic effect was observed in the subjects with concurrent diseases of the otorhinolaryngological (ENT) organs, abusing drinks, and having significant long-term, nutrition disorders.

Download this pdf

Antioxidant Small Phenolic Ingredients in Inonotus obliquus - Yuki NAKAJIMA et.al. - Niigata University of Pharmacy and Applied Life Science; Higashijima, Niigata 956–8603, Japan. © (2007) The authors.

Abstract - Inonotus obliquus (persoon) Pilat (Chaga, in Russia, kabanoanatake in Japan) is a fungus having been used as a folk medicine in Russia and said to have many health beneficial functions such as immune modulating and anti-cancer activities. In the present study, the antioxidant activity of hot water extract (decoction) of Chaga was precisely compared with those of other medicinal fungi (Agaricus blazei Mycelia, Ganoderma lucidum and Phellinus linteus) showing Chaga had the strongest antioxidant activity among fungi examined in terms of both superoxide and hydroxyl radicals scavenging activities. Further determination of the antioxidant potential of isolated fruiting body (brown part) and Sclerotium (black part) revealed the 80% MeOH extract of fruiting body had the highest potential as high as that of Chaga decoction. Finally, seven antioxidant components were isolated and purified from the 80% MeOH extract of Chaga fruiting body, and their chemical structures were determined as small phenolics as follows: 4-hydroxy-3,5-dimethoxy benzoic acid 2-hydroxy-1-hydroxymethyl ethyl ester (BAEE), protocatechic acid (PCA), caffeic acid (CA), 3,4-dihybenzaladehyde (DB), 2,5-dihydroxyterephtalic acid (DTA), syringic acid (SA) and 3,4-dihydroxybenzalacetone (DBL). Notably, BAEE was assigned as the new compound firstly identified from the natural source in the present study.

Download this pdf

Identification of Inonotus obliquus (Chaga) and Analysis of Antioxidation and Antitumor Activities of Polysaccharides - Yana Song et.al. - © (2008) The authors.

Abstract Inonotus obliquus, a wild wood-decay fungus which grows on birch trees in cool climates, has a variety of biological activities that the scientific community is paying more and more attention to. However, the research work is moving at a snail's pace. The methods of strain identification and the hypha microstructure have not been reported. We isolated one strain of filamentous molds from fruit body which was collected from birch wood on Changbai Mountain, cultivated mycelia on an inclined plane, and examined its micro morphology based on macroscopic examination. The strain was identified as I. obliquus by sequencing its ITS (internal transcribed spacer) domain. We subsequently investigated some of the mycelium polysaccharides' biological activities. The strain used in this study as the producers of anti oxidation and anti- cancer polysaccharides was LNUF008. After fermentation in a 30-L fermenter, mycelia were obtained. The polysaccharides were extracted by transonic recirculation and ethanol precipitation. In order to identify the anti oxidation effect, we designed an assay to test the inhibition of endogenous and Fe2+-Cys-induced lipid peroxidation as well as ferrous sulfate/ascorbate (Fe2+-VC)-induced mitochondrial swelling. The MTT [3-(4,5-dimethylthiazol-2- yl)-2,5-diphenyltetrazolium bromide] method was used to study the anti proliferation activity of the polysaccharides on SMMC7721 hepatoma cells. The results indicate that I. obliquus polysaccharides exhibit high anti tumor and anti oxidation effects. The submerged culture method of growing I. obliquus will enable large-scale production of the polysaccharides.

Download this pdf

Sterol composition in field-grown and cultured mycelia of Inonotus Obliquus - Zheng Wei-fa, et.al. - Key laboratory for biotechnology on Medicinal plants, Xuzhou, China © 2006 the authors.

Abstract - Sterols are one of the active classes of compounds in Inonotus obliquus for their effective therapy of many diseases. In field environment, this fungus accumulates large amount of sterols. In cultured mycelia, however, this class of compounds is less accumulated. For analyzing the factors responsible for differing sterol composition, the field-grown and cultured mycelia were extracted with 80% ethanol at room temperature and total sterols were prepared using silicon gel column chromatography followed by identification using either GC-MS or spectroscopic methods. The results suggested that the sterol composition in mycelia of the fungus can be diversified by supplementing substances inhibiting enzymatic process towards the synthesis of ergosterol. Harsh growth conditions in field environment (i. e. temperature variation, UV irradiation etc.) can delay the synthesis of ergosterol and hereby diversify the sterol composition in the mycelia of Inonotus obliquus.

Download this pdf

Chemical and pharmacological properties of dry extract from black birch fungus - G. L. Ryzhova, et. al. - Khimiko-Farmatsevticheskii Zhurnal, Vol. 31, No. I0, pp. 44-47, October, 1997 © (1994) The authors.

Abstract - Black birch fungus (Inonotus obliquus f sterilis, known in Russia as "chaga") is used in folk medicine for the treatment of gastrointestinal tract disorders. Since 1955, a dense extract of this fungus has been produced on the commercial level and used in medical practice as the drug befungin. The purpose of this work was to study the chemical composition and pharmacological properties of the total dry black birch fungus extract (DBFE), prepared according to a new patented technology [1], and the individual biologically active fractions.

Download this pdf

Antitumor Activity of Water Extract of a Mushroom, Inonotus obliquus, against HT-29 Human Colon Cancer Cells - Sung Hak Lee, et.al. - PHYTOTHERAPY RESEARCH © (2009) The authors.

Abstract - In the current study, it was demonstrated that the hot water extract of I. obliquus (IOWE) exerts inhibitory activity against the proliferation of human colon cancer cells (HT-29). The inhibitory effect of IOWE on the growth of HT-29 cancer cells was evaluated by treating cells with IOWE at concentrations of 0.25, 0.5 and 1.0 mg/mL for 24 or 48 h. The IOWE inhibited cell growth in a dose-dependent manner, and this inhibition was accompanied by apoptotic cell death. The maximum inhibitory effect (56%) was observed when IOWE was treated at a concentration of 1.0 mg/mL for 48 h. The apoptotic effect of IOWE on HT-29 cells was also confirmed by flow cytometric analysis. In addition, the apoptotic cell percentage was closely associated with down-regulation of Bcl-2 and up-regulation of Bax and caspase-3. The results suggest that IOWE 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 down-regulation of anti-apoptotic proteins.

Download this pdf

Antioxidant effect of Inonotus obliquus - Yong Cui, et.al. - Journal of Ethnopharmacology 96 (2005) 79–85 © (2005) The authors.

Abstract - The mushroom Inonotus obliquus (Fr.) Pilát (Hymenochaetaceae), has been widely used as a folk medicine in Russia, Poland and most of the Baltic countries. The purpose of this study was to elucidate the antioxidant capacities of Inonotus obliquus. Four extracts from the fungus were evaluated for antioxidant activity against the 1,1-diphenyl-2-picrylhydrazyl (DPPH), superoxide, and peroxyl radicals. The polyphenolic extract had a strong antioxidant activity, and the extract containing triterpenoids and steroids presented a relatively strong antioxidant effect. The polysaccharide extract, however, was inactive. The protective effects of these four extracts were assessed against hydrogen peroxide-induced oxidative stress using a human keratinocyte cell line, HaCaT. Our results show that the polyphenolic extract protected these cells against hydrogen peroxide-induced oxidative stress, while the polysaccharide, triterpenoid and steroid extracts were ineffective. Additionally, the remnant polyphenolic and low molecular weight polysaccharide extracts showed a weakly protective effect at a concentration of 50 􏰀g/ml. Our results indicate that Inonotus obliquus has the capacity to scavenge free radicals at concentrations higher than 5 􏰀g/ml and that the polyphenolic extract can protect cells against oxidative stress.

Download this pdf

Antimutagenic effects of subfractions of Chaga mushroom (Inonotus obliquus) extract - Seung-Shi Ham, et.al. - Mutation Research 672 (2009) 55–59 © (2008-2009) The authors.

Abstract - Inonotus obliquus is a mushroom commonly known as Chaga that is widely used in folk medicine in Siberia, North America, and North Europe. Here, we evaluated the antimutagenic and antioxidant capacities of subfractions of Inonotus obliquus extract. The ethyl acetate extract was separated by vacuum chromatography into three fractions, and the fraction bearing the highest antimutagenic activity was subsequently separated into four fractions by reversed phase (ODS-C18) column chromatography. The most antimutagenic fraction was then separated into two subfractions (subfractions 1 and 2) by normal phase silica gel column chromatography. Ames test analysis revealed that the subfractions were not mutagenic. At 50 􏰀g/plate, subfractions 1 and 2 strongly inhibited the mutagenesis induced in Salmonella typhimurium strain TA100 by the directly acting mutagen MNNG (0.4 􏰀g/plate) by 80.0% and 77.3%, respectively. They also inhibited 0.15 􏰀g/plate 4NQO-induced mutagenesis in TA98 and TA100 by 52.6–62.0%. The mutagenesis in TA98 induced by the indirectly acting mutagens Trp-P-1 (0.15 􏰀g/plate) and B(􏰁)P (10 􏰀g/plate) was reduced by 47.0–68.2% by the subfractions, while the mutagenesis in TA100 by Trp-P-1 and B(􏰁)P was reduced by 70.5–87.2%. Subfraction 1 was more inhibitory than subfraction 2 with regard to the mutagenic effects of 4NQO, Trp-P-1, and B(􏰁)P. Subfractions 1 and 2 also had a strong antioxidant activity against DPPH radicals and were identified by MS, 1H NMR and 13C NMR analyses as 3􏰂-hydroxy-lanosta-8, 24- dien-21-al and inotodiol, respectively. Thus, we show that the 3􏰂-hydroxy-lanosta-8, 24-dien-21-al and inotodiol components of Inonotus obliquus bear antimutagenic and antioxidative activities.

Download this pdf

Analysis of an aqueous extract of Inonotus Obliquus (Chaga) - WITOLD MAZURKIEWICZ - Drug Research, Vol. 63 No. 6 pp. 497-501, 2006 © (2006) The author.

Abstract - Water-soluble melanin complexes were extracted with hot water from Inonotus obliquus fungus. They were characterized before and after reaction with diluted hydrochloric acid. The organic components as products of degradation of melanin complexes were separated by column chromatography and analyzed by GC-MS method.

Download this pdf

The Anticancer Effect of Inonotus obliquus Pilat (Chaga) Processed by Nanomill Technology In vivo - Dong-Heui Kim, et.al. - Korean J. Microscopy 39(2), 125~132(2009) © (2008-2009) The authors.

Abstract - Extracts and fractions of Inonotus obliquus (Chaga in Russia) have been known to have various biological activities, including antimutagenic, anticancer, antioxidative, and immunostimulating effects. This study was performed to confirm anticancer effect of 10% superfine Chaga mushroom processed by nano-mill technology on C57BL/6 mice. Chaga parti- cles belonged in the size of 1 μm was about 40% after nanomill processing according to the volume distribution. As the result of subcutaneous injection of B16BL6 melanoma cells to the mice, the tumor volume (p⁄0.001) and tumor weight (p⁄0.01) was significantly decreased in the experimental (NCh) group as compared with control (C) group and the tumor growth inhibitory rate was 29.2%. On examination of survival rate after intraperitoneal injection of B16BL6 melanoma cells, the mean survival time per a mouse was 17.7 and 26.0 days in C and NCh group respectively. The survival rate of NCh group was 40% when that of C group was 0% at the 35th day. On the result of examination to confirm histological toxicity by Chaga superfine particles, both groups did not show any morphological and pathological changes in the small and large intestine under the light microscope. These results suggest that feeding of superfine Chaga produced by nano- mill technique has a tumor growth inhibitory effect in vivo.

Download this pdf

Chaga and Other Fungal Resources - Assessment of Sustainable Commercial Harvesting in Khabarovsk and Primorsky Krais, Russia - David Pilz - Assessment report © (2004) The author.

Abstract - Sources of information on chaga harvesting are scarce, especially in the English literature, and few sources of data exist on chaga abundance or harvest levels, so this report represents one of the first summaries of these topics in the English language. References are cited where particular facts or important points are noted. The report was developed during one week of library research, two weeks of travel to Khabarovsk and Vladivostock Russia to meet key individuals, and one week of preparation.

Download this pdf

Chemical and medico-biological properties of Chaga - M. Ya. Shashkina, et.al. - Pharmaceutical Chemistry Journal Vol. 40, No. 10, 2006 © (2006) The authors.

Abstract - Data on the chemical composition and pharmacological activity of chaga (Inonotus obliquus) are reviewed. The possible mechanisms of action and factors responsible for the discrepancy of data available in the litera- ture are discussed. The physical and chemical characteristics of melanin (polyphenolic chromogenic humin-like complex present in chaga) and its role in the regulation of physiological processes are considered.

Download this pdf

Fungal medicine, Fuscoporia obliqua (Chaga), as a traditional herbal medicine: its bioactivities, in vivo testing and medicinal effects - Tomiyasu Koyama, et.al. - Asian Biomedicine Vol. 2 No. 6 December 2008; 459-469 © (2008) The author.

Abstract - Fuscoporia obliqua is a kind of mushroom growing on silver birch. In northern terrains of Asia, Fuscoporia has been used as a traditional herbal medicine for a long period. However, its therapeutic actions were little studied until recently. Scientific research has now begun on the biological function and mechanism of action of Fuscoporia extracts. This study reveals Fuscoporia active compounds, in vivo testing and medicinal effects, referring to recent studies on other mushroom species.

Download this pdf

Phenolic compounds from Inonotus obliquus and their immune-stimulating effects - ZHENG Wei-Fa, et.al., - Mycosystema 27(4) p.574-581 © (2008) The author.

Abstract - Phenolic compounds from field-grown Inonotus obliquus sclerotia (Chaga) consist mainly of hispidin analogs and melanins, and are thought to be the active constituents to treat several human diseases. In submerged cultures of the fungus, however, no information is currently available on the production of phenolic compounds and their corresponding pharmacological functions. In this study, phenolic compounds from Chaga and submerged cultures of the fungus were assayed for their composition and immune-stimulating effects. Phenolic compounds produced by I. obliquus in submerged cultures mostly consist of flavonoids, together with small amounts of hispidin analogs and melanins. This is quite contrary to the situation in Chaga, where flavonoids are determined as trace elements. Furthermore, phenolic compounds from Chaga show capacity about two-fold higher than those produced in submerged cultures in inhibiting cyclophosphamide-induced reduction of bodyweight, spleen index and viability of peripheral lymphocytes in test mice. Thus less production of hispidin analogs and melanins is likely to be responsible for less immune-stimulating effects in phenolic compounds from submerged cultures, and additional factors should be imposed during submerged cultures of I. obliquus to regulate biosynthesis of phenolic compounds directed to the composition similar to Chaga.

Download this pdf

The scientific rediscovery of an ancient Chinese herbal medicine- Cordyceps sinensis: part 1 - JIA-SHI ZHU, et.al. (15 pages)

Abstract - This review presents Cordyceps sinensis (Berk.) Sacc., a fungus highly valued in China as a tonic food and herbal medicine. The extant records show the continued use of C. sinensis is now centuries old. The major chemical, pharmacological, and toxicological studies on C. sinensis and the various derived, cultured, fermented mycelial products currently in use are reviewed from the English and Chinese literature. Preclinical in vitro and in vivo studies and clinical blinded or open-label trials in to date over 2000 patients are reviewed. These studies show the main activities of the fungus in oxygen-free radical scavenging, antisenescence, endocrine, hypolipidemic, antiatherosclerotic, and sexual function-restorative activities. The safety of the fungus, its effects on the nervous system, glucose metabolism, the respiratory, hepatic, cardiovascular, and immune systems, immunologic disease, inflammatory conditions, cancer, and diseases of the kidney will be reviewed in the second part of this article to be published in winter 1998.

Download this pdf

The scientific rediscovery of an ancient Chinese herbal medicine- Cordyceps sinensis; part 2 - JIA-SHI ZHU, et.al. (29 pages)

Abstract - Cordyceps sinensis (Berk.) Sacc., is a time-honored tonic food and herbal medicine in China, where recent research has shown that many of its traditional uses may be viewed from the basis of pharmacological activities. The ongoing exploration of C. sinensis in its wild form and cultured, fermented mycelial products derived from it, are reviewed from English and Chinese literature. Part II concludes the series with a review of C. sinensis in preclinical in vitro and in vivo studies, and open-label and double-blinded clinical trials on the respiratory, renal, hepatic, cardiovascular, immunologic, and nervous systems, and its effects on cancer, glucose metabolism, inflammatory conditions, and toxicological studies. In Part I, which appeared in autumn 1998, we discussed the effects of C. sinensis on antisenescence, endocrine and sexual functions, atherosclerosis, hyperlipidemia, and free radicals.

Download this pdf

Pharmacological Functions of Chinese Medicinal Fungus Cordyceps sinensis and Related Species - SHENG-YUAN WANG, et.al. (10 pages)

Abstract - Cordyceps sinensis, an entomogenous fungus used in traditional Chinese medicine, exhibits very broad biological and pharmacological actions in hepatic, renal, cardiovascular, and immunologic systems as well as anticancer activity. Pharmacological functions of Cordyceps are primarily due to the bioactive polysaccharides, modified nucleosides, and cyclosporin-like metabolites produced by this fungus and related species. The beneficial effects on renal and hepatic function and immunomodulation-related antitumor activities are most promising and deserve great attention. Many previous studies used fruiting bodies, but recently an increasing number of studies have used cultured mycelia in investigations. It is difficult to determine if the same bioactive ingredients exist in fruiting bodies and cultured mycelia and contribute to the pharmacological actions reported in the literature. More mechanism-based, disease-oriented pharmacologi- cal studies are required to ensure clinical efficacy for particular diseases. Adjuvant therapy using C. sinensis for immune function distur- bances, cancer, and renal failure is possible if double-blind, randomized placebo-control clinical studies show the efficacy of this herb.

Download this pdf

Quality control of Cordyceps sinensis, a valued traditional Chinese medicine - S.P. Li et.al. (14 pages)

Abstract - Cordyceps sinensis, a well-known and valued traditional Chinese medicine, is also called DongChongXiaCao (winter worm summer grass) in Chinese. It is commonly used to replenish the kidney and soothe the lung for the treatment of fatigue, night sweating, hyposexualities, hyperglycemia, hyperlipidemia, asthemia after severe illness, respiratory disease, renal dysfunction and renal failure, arrhythmias and other heart disease, and liver disease. As the rarity and upstanding curative effects of natural Cordyceps, several mycelial strains have been isolated from natural Cordyceps and manufactured in large quantities by fermentation technology, and they are commonly sold as health food products in Asia. In addition, some substitutes such as Cordyceps militaris also have been used and adulterants also confused the market. Therefore, quality control of C. sinensis and its products is very important to ensure their safety and efficacy. Herein, markers and analytical methods for quality control of Cordyceps were reviewed and discussed.

Download this pdf

Effects of a supplement designed to increase ATP levels on muscle strength, power output, and endurance - Trent J Herda et.al. (5 pages)

Abstract
Background: The present study examined the acute effects of a nutritional supplement intended to improve adenosine triphosphate (ATP) concentrations on vertical jump height, isometric strength of the leg extensors, leg extension endurance, and forearm flexion endurance.
Methods: Twenty-four healthy men (mean age � SD = 23 � 4 yrs, stature = 181 � 7 cm, and body mass = 82 � 12 kg) volunteered to complete a familiarization trial plus 2 randomly-ordered experimental trials separated by a 7-day washout period. Participants received either 6 (body mass < 91 kg) or 8 (body mass � 91 kg) tablets of the treatment (TR; 625 mg of adenylpyrophosphoric acid and calcium pyruvate, 350.8 mg of cordyceps sinensis extract and yohimbine hydrochloride) or placebo (PL; 980 mg of microcrystalline cellulose) 1 hour prior to the following tests: countermovement vertical jump (CVJ), forearm flexion repetitions to exhaustion, isometric maximal voluntary contractions (MVCs) of the leg extensors, and a 50-repetition maximal concentric isokinetic leg extension endurance test.
Results: There were no differences between the TR and PL trials for CVJ height (P > 0.05), isometric MVC peak torque (P > 0.05), maximal concentric isokinetic peak torque (P > 0.05), percent decline during the leg extension endurance tests (P > 0.05), or repetitions to exhaustion during the forearm flexion endurance tests (P > 0.05).
Conclusion: These findings indicated no improvements in the measured variables as a result of ingesting this nutritional supplement. Future studies should examine whether chronic supplementation or a loading period is necessary to observe any ergogenic effects of this supplement.

Download this pdf

Genetic diversity of Ophiocordyceps sinensis, a medicinal fungus endemic to the Tibetan Plateau: Implications for its evolution and conservation - Yongjie Zhang et.al. (12 pages)

Abstract
Background: Ophiocordyceps sinensis (syn. Cordyceps sinensis), endemic to alpine regions on the Tibetan plateau, is one of the most valuable medicinal fungi in the world. Huge commercial demand has led to excessive harvest and a dramatic decline in its numbers. The diversity of terrains and climates on the Tibetan Plateau and the broad insect host range (more than 50 species in the family Hepialidae) may have resulted in substantial intraspecific genetic diversity for this fungus. The objective of this study was to evaluate the population distribution of O. sinensis from geographically diverse regions of the Tibetan Plateau based on nrDNA ITS and MAT1-2-1 gene sequences. Understanding of the genetic diversity and genesis of O. sinensis will provide important information for the evolution and conservation of this fungus.
Results: Significant sequence variations in the ITS and MAT1-2-1 genes (27 and 23 informative sites, eight and seven haplotypes, respectively) were observed. Phylogenetic analysis based on ITS sequences, MAT1-2-1 sequences, or their combined data set, clustered isolates from northern regions in one clade (clade I), whereas isolates from southern regions were dispersed in all four clades (clade I-IV). Single-strand conformation polymorphism (SSCP) analyses of 2639 ITS clones from seven samples revealed 91 different SSCP patterns that were subsequently sequenced. ITS heterogeneity was found in XZ-LZ07-H1 (Nyingchi population), and 17 informative sites and five haplotypes were detected from 15 clones. The five haplotypes clustered into three clades (clade I, II, and IV).
Conclusions: Significant genetic divergence in O. sinensis was observed and the genetic diversification was greater among southern isolates than that among northern isolates. The polymorphism of nrDNA ITS sequences suggested that O. sinensis spread from a center of origin (the Nyingchi District) to southern regions and subsequently to northern areas. These results suggest that southern populations are important reservoirs of genetic diversity and should be taken into account in conservation programs.

Download this pdf

Last Stand for the Body Snatcher Of the Himalayas? - Richard Stone. - Science, Vol. 322 Nov 2008 © (2008) The author.

Abstract - Some people kill for it. Others risk their lives for it. To many, it’s the creepiest thing they’ve ever seen. It is Cordy- ceps sinensis, a parasitic fungus that consumes its host, ghost moth caterpillars, from inside out as they hibernate in alpine meadows in the Himalayas and on the Tibetan Plateau.

Download this pdf

Cordyceps sinensis - Health Supplement Enhances Recovery from Taxol-Induced Leukopenia - Wei-Chung Liu, et.al. - Exp Biol Med (Maywood). 2008 April ; 233(4): 447–455 © (2008) The authors.

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

Download this pdf

Hericium erinaceus- an edible mushroom with medicinal values - Asaduzzaman Khan, et.al. (6 pages)© (2013) The authors.

Abstract - Mushrooms are considered as nutritionally functional foods and source of physiologically beneficial medicines. Hericium erinaceus, also known as Lion’s Mane Mushroom or Hedgehog Mushroom, is an edible fungus, which has a long history of usage in traditional Chinese medicine. This mushroom is rich in some physiologically important components, especially β-glucan polysacchar- ides, which are responsible for anti-cancer, immuno-mod- ulating, hypolipidemic, antioxidant and neuro-protective activities of this mushroom. H. erinaceus has also been reported to have anti-microbial, anti-hypertensive, anti- diabetic, wound healing properties among other thera- peutic potentials. This review article has overviewed the recent advances in the research and study on H. erinaceus and discussed the potential health beneficial activities of this mushroom, with the recognition of bioactive compounds responsible for these medicinal properties.

Download this pdf

Effects of cultivation techniques and processing on antimicrobial and antioxidant activities of Hericium erinaceus - Kah Hui Wong, et. al. (10 pages)© (2009) The authors.

Abstract - Hericium erinaceus, a temperate mushroom, is currently cultivated in Malaysia. As cultivation and processing conditions may affect the medicinal properties, antimicrobial and antioxidant properties of locally grown H. erinaceus have been investigated.

The fruitbodies that were fresh, oven-dried or freeze-dried were extracted with methanol. Their properties were compared to those exhibited by mycelium extract of the same mushroom. Various extracts of H. erinaceus inhibited the growth of pathogenic bacteria but not of the tested fungus.

Mycelium extract contained the highest total phenolic content and the highest ferric reducing antioxidant power (FRAP). The fresh fruitbody extract showed the most potent 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity. However, oven-dried fruitbody extract was excellent in reducing the extent of b-carotene bleaching.

The total phenolic content and total antioxidant activity in the oven-dried fruitbody extract was high compared to the freeze-dried or fresh fruitbody extract. This may be due to generation and accumulation of Maillard’s reaction products (MRPs), which are known to have antioxidant properties.

Thus, the consumption of H. erinaceus fruitbody grown in tropical conditions may have health promoting benefits. Furthermore, the production of H. erinaceus mycelium in submerged cultures may result in standardized antioxidant formulation for either human nutrition or therapy.

Hence, it has been shown that the processing of fruitbody and not the cultivation conditions affects the selected bioactive properties of H. erinaceus.

Download this pdf

Compounds for dementia from Hericium erinaceum - Tzeng Tsai-Teng, et. al. (7 pages)© (2008) The authors.

Abstract - Our group has been conducting a search for compounds for dementia derived from medicinal mushrooms since 1991. A series of benzyl alcohol derivatives (named hericenones C to H), as well as a series of diterpenoid derivatives (named erinacines A to I) were isolated from the mushroom Hericium erinaceum.

These compounds significantly induced the synthesis of nerve growth factor (NGF) in vitro and in vivo. In a recent study, dilinoleoyl-phosphatidylethanolamine (DLPE) was isolated from the mushroom and was found to protect against neuronal cell death caused by β-amyloid peptide (Aβ) toxicity, endoplasmic reticulum (ER) stress and oxidative stress.

Furthermore, the results of preliminary clinical trials showed that the mushroom was effective in patients with dementia in improving the Functional Independence Measure (FIM) score or retarding disease progression.

Download this pdf

Reversal of cognitive decline: A novel therapeutic program - Tsai-Teng, et. al. (11 pages)© (2015) The authors.

Abstract - This report describes a novel, comprehensive, and personalized therapeutic program that is based on the underlying pathogenesis of Alzheimer’s disease, and which involves multiple modalities designed to achieve metabolic enhancement for neurodegeneration (MEND).

The first 10 patients who have utilized this program include patients with memory loss associated with Alzheimer’s disease (AD), amnestic mild cognitive impairment (aMCI), or subjective cognitive impairment (SCI).  Nine of the 10 displayed subjective or objective improvement in cognition beginning within 3‐6 months, with the one failure being a patient with very late stage AD.

Six of the patients had had to discontinue working or were struggling with their jobs at the time of presentation, and all were able to return to work or continue working with improved performance.   Improvements have been sustained, and at this time the longest patient follow‐up is two and one‐half years from initial treatment, with sustained and marked improvement.

These results suggest that a larger, more extensive trial of this therapeutic program is warranted. The results also suggest that, at least early in the course, cognitive decline may be driven in large part by metabolic processes.  Furthermore, given the failure of monotherapeutics in AD to date, the results raise the possibility that such a therapeutic system may be useful as a platform on which drugs that would fail as monotherapeutics may succeed as key components of a therapeutic system.

Download this pdf

Hericenones and erinacines- stimulators of nerve growth factor (NGF) biosynthesis in Hericium erinaceus - Bing-Ji Ma et.al. (8 pages)© (2010) The authors.

Abstract - This review surveys the chemical and biological literature dealing with the isolation, structural elucidation and bioactivity of hericenones and erinacines from the fruiting body and mycelium of Hericium erinaceus, concentrating on work that has appeared in the literature up to December 2009.

Download this pdf

Reduction of depression and anxiety after 4 weeks of Lion's Mane intake - Mayumi Nagano et. al. (7 pages)© (2010) The authors.

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

Download this pdf

Functional Recovery Enhancement Following Injury to Rodent Peroneal Nerve by Lion’s Mane Mushroom, Hericium erinaceus - Kah-Hui Wong et.al. (12 pages)© (2009) The authors.

Abstract - Peripheral nerve injury represents a huge burden to society. Following peripheral nerve injury, improved behavioral outcome may be the most important evidence of functionality of axonal regeneration after any repair strategy. Nerve-crush injury is a well-established axonotmetic model in experimental regeneration studies to investigate the impact of various pharmacological treatments. Hericium erinaceus is a temperate mushroom but is now being cultivated in tropical Malaysia. In this study, we investigated the activity of aqueous extract of H. erinaceus fresh fruitbodies in promoting functional recovery following an axonotmetic peroneal nerve injury in adult female Sprague-Dawley rats with a long-term view toward the possible use of this mushroom in the treatment of nerve injury. Functional recovery was assessed in the behavioral experiment by walking-track analysis and toe- spreading reflex. The peroneal functional index (PFI) was determined before surgery and after sur- gery, as the rats showed signs of recovery. Analysis of the PFI indicated that the return of hind-limb function occurred by day 10 to 14 and by day 14 to 17 in the treated and control (nontreated) groups, respectively. Normal toe-spreading in the crushed limb was achieved by day 7 to 10 and day 12 to 17 in the treated and control group, respectively. These results suggest that daily administration of aqueous extract of H. erinaceus fresh fruitbodies has a beneficial effect on the recovery of injured rat peroneal nerve in the early stages of regeneration. The PFI and toe-spreading reflex improved faster in the treated group than in the nontreated group.

Download this pdf

Improving Effects of the Mushroom Yamabushitake (Hericium erinaceus) on Mild Cognitive Impairment- A Double-blind Placebo-controlled Clinical Trial - Koichiro Mori et. al. (6 pages)© (2008) The authors.

Abstract - A double-blind, parallel-group, placebo-controlled trial was performed on 50- to 80-year-old Japanese men and women diagnosed with mild cognitive impairment in order to examine the efficacy of oral administration of Yamabushitake (Hericium erinaceus), an edible mushroom, for improving cognitive impairment, using a cognitive function scale based on the Revised Hasegawa Dementia Scale (HDS-R). After 2 weeks of preliminary examination, 30 subjects were randomized into two 15-person groups, one of which was given Yamabushitake and the other given a placebo. The subjects of the Yamabushitake group took four 250 mg tablets containing 96% of Yamabushitake dry powder three times a day for 16 weeks. After termination of the intake, the subjects were observed for the next 4 weeks. At weeks 8, 12 and 16 of the trial, the Yamabushitake group showed significantly increased scores on the cognitive function scale compared with the placebo group. The Yamabushitake group’s scores increased with the duration of intake, but at week 4 after the termination of the 16 weeks intake, the scores decreased significantly. Laboratory tests showed no adverse effect of Yamabushitake. The results obtained in this study suggest that Yamabushitake is effective in improving mild cognitive impairment.

Download this pdf

Hypoglycemic effect of extract of Hericium erinaceus - Jinn Chyi Wang, et. al. (6 page)© (2005) The authors.

Abstract - Recent studies have determined that many types of mushroom (eg Hericium spp), may have important physiological functions in humans, including antioxidant activities, the regulation of blood lipid levels and reduction of blood glucose levels. In this study, a methanol extract of the fruiting bodies of Hericium erinaceus was adsorbed on silica gel columns and eluted using polarity gradients of chloroform/ethyl acetate/acetone/methanol. The major components of the extract were D-threitol, D-arabinitol and palmitic acid identified by their chromatographic profiles and spectroscopic characteristics. The methanol extract of H erinaceus was concentrated to remove solvent yielding a residue (referred to as HEM) which was added to the diet. The hypoglycemic effects of feeding HEM to streptozotocin-induced diabetic rats were studied. Polydipsia was stronger in induced diabetic rats not fed HEM than in those receiving HEM. Rats fed with HEM had significantly lower elevation rates of blood glucose level than those not fed with HEM. The effects on blood glucose, serum triglyceride and total cholesterol levels were more significant in the rats fed daily with HEM at doses of 100 mg kg−1 body weight (bw) rather than 20 mg kg−1 bw (p < 0.05).

Download this pdf

The influence of Hericium erinaceus extract on myelination process in vitro - E.V. Kolotushkina, et. al. (8 pages)© (2003) The authors.

Abstract - Myelin sheathes, wrapping axons, perform the following important functions: support, protection, feeding and isolation. Injury of myelin compact structure leads to an impairment and severe illness of the nerve system.

Exact mechanisms underlying the myelination process and myelin sheaths damage have not been established yet. Therefore search for substances, which provide regulatory and protective effects on the normal myelination as well as stimulating action on the remyelination after myelin damage, is of special interest.

Recently it was shown that extract from mushroom Hericium erinaceus had an activating action on the nerve tissue. So the aim of the present work was to study an influence of an extract from H. erinaceus on the cerebellar cells and the process of myelination in vitro.

Obtained data revealed the normal growth of the nerve and glial cells with extract at cultivating. No pathologic or toxic action of the extract has been found. The cell ultrastructure was intact and similar to that observed in vivo. The process of myelination in the presence of the extract began earlier as compared to controls and was characterised by a higher rate.

Thus, extract of H. erinaceus promoted normal development of cultivated cerebellar cells and demonstrated a regulatory effect on the process of myelin genesis process in vitro.

Download this pdf

Protective Effects of Hericium erinaceus Mycelium and Its Isolated Erinacine A against Ischemia-Injury-Induced Neuronal Cell Death - Kam-Fai Lee, et. al. (17 pages)© (2014) The authors.

Abstract - Hericium erinaceus, an edible mushroom, has been demonstrated to potentiate the effects of numerous biological activities. The aim of this study was to investigate whether H. erinaceus mycelium could act as an anti-inflammatory agent to bring about neuroprotection using a model of global ischemic stroke and the mechanisms involved.

Rats were treated with H. erinaceus mycelium and its isolated diterpenoid derivative, erinacine A, after ischemia reperfusion brain injuries caused by the occlusion of the two common carotid arteries. The production of inflammatory cytokines in serum and the infracted volume of the brain were measured.

The proteins from the stroke animal model (SAM) were evaluated to determine the effect of H. erinaceus mycelium. H. erinaceus mycelium reduced the total infarcted volumes by 22% and 44% at a concentration of 50 and 300 mg/kg, respectively, compared to the SAM group. The levels of acute inflammatory cytokines, including interleukin-1β, interleukin-6 and tumor necrosis factor á, were all reduced by erinacine A.

Levels of nitrotyrosine-containing proteins, phosphorylation of p38 MAPK and CCAAT enhancer-binding protein (C/EBP) and homologous protein (CHOP) expression were attenuated by erinacine A. Moreover, the modulation of ischemia injury factors present in the SAM model by erinacine A seemed to result in the suppression of reactive nitrogen species and the downregulation of inducible NO synthase (iNOS), p38 MAPK and CHOP.

These findings confirm the nerve-growth properties of Hericium erinaceus mycelium, which include the prevention of ischemic injury to neurons; this protective effect seems to be involved in the in vivo activity of iNOS, p38 MAPK and CHOP.

Download this pdf

Hericium erinaceus mycelium and its isolated erinacine A protection from MPTP-induced neurotoxicity through the ER stress - Hsing‑Chun Kuo1, et. al. (14 pages)© (2016) The authors.

Abstract - Background: Hericium erinaceus is an edible mushroom; its various pharmacological effects which have been investi‑ gated. This study aimed to demonstrate whether efficacy of oral administration of H. erinaceus mycelium (HEM) and its isolated diterpenoid derivative, erinacine A, can act as an anti-neuroinflammatory agent to bring about neuroprotec‑ tion using an MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) mouse model of Parkinson’s disease, which results in motor disturbances, in addition to elucidating the mechanisms involved.

Methods: Mice were treated with and without HEM or erinacine A, after MPTP injection for brain injuries by the degeneration of dopaminergic nigrostriatal neurons. The efficacy of oral administration of HEM improved MPTPinduced loss of tyrosine hydroxylase positive neurons and brain impairment in the substantia nigra pars compacta as measured by brain histological examination.

Results: Treatment with HEM reduced MPTP-induced dopaminergic cell loss, apoptotic cell death induced by oxidative stress, as well as the level of glutathione, nitrotyrosine and 4-hydroxy-2-nonenal (4-HNE). Furthermore, HEM reversed MPTP-associated motor deficits, as revealed by the analysis of rotarod assessment. Our results demonstrated that erinacine A decreases the impairment of MPP-induced neuronal cell cytotoxicity and apoptosis, which were accompanied by ER stress-sustained activation of the IRE1α/TRAF2, JNK1/2 and p38 MAPK pathways, the expression of C/EBP homologous protein (CHOP), IKB-β and NF-κB, as well as Fas and Bax.

Conclusion: These physiological and brain histological changes provide HEM neuron-protective insights into the progression of Parkinson’s disease, and this protective effect seems to exist both in vivo and in vitro.

Download this pdf

Erinacine A-Enriched Hericium erinaceus Mycelium Produces Antidepressant-Like Effects through Modulating BDNF/PI3K/Akt/GSK-3β Signaling in Mice - Chun-Hung Chiu, et. al. (21 pages)© (2018) The authors.

Abstract - Antidepressant-like effects of ethanolic extract of Hericium erinaceus (HE) mycelium enriched in erinacine A on depressive mice challenged by repeated restraint stress (RS) were examined.

HE at 100, 200 or 400 mg/kg body weight/day was orally given to mice for four weeks. After two weeks of HE administration, all mice except the control group went through with 14 days of RS protocol. Stressed mice exhibited various behavioral alterations, such as extending immobility time in the tail suspension test (TST) and forced swimming test (FST), and increasing the number of entries in open arm (POAE) and the time spent in the open arm (PTOA).

Moreover, the levels of norepinephrine (NE), dopamine (DA) and serotonin (5-HT) were decreased in the stressed mice, while the levels of interleukin (IL)-6 and tumor necrosis factor (TNF)-α were increased.

These changes were significantly inverted by the administration of HE, especially at the dose of 200 or 400 mg/kg body weight/day. Additionally, HE was shown to activate the BDNF/TrkB/PI3K/Akt/GSK-3β pathways and block the NF-κB signals in mice.

Taken together, erinacine A-enriched HE mycelium could reverse the depressive-like behavior caused by RS and was accompanied by the modulation of monoamine neurotransmitters as well as pro-inflammatory cytokines, and regulation of BDNF pathways.

Therefore, erinacine A-enriched HE mycelium could be an attractive agent for the treatment of depressive disorders.

Download this pdf

Erinacine A-enriched Hericium erinaceus mycelium ameliorates Alzheimer’s disease-related pathologies - Tzeng Tsai-Teng, et. al. (12 pages)© (2016) The authors.

Abstract - Background: The fruiting body of Hericium erinaceus has been demonstrated to possess anti-dementia activity in mouse model of Alzheimer’s disease and people with mild cognitive impairment. However, the therapeutic potential of Hericium erinaceus mycelia on Alzheimer’s disease remains unclear. In this study, the effects of erinacine A-enriched Hericium erinaceus mycelia (HE-My) on the pathological changes in APPswe/PS1dE9 transgenic mouse model of Alzheimer’s disease are studied.

Results: After a 30 day oral administration to 5 month-old female APPswe/PS1dE9 transgenic mice, we found that HE-My and its ethanol extracts (HE-Et) attenuated cerebral Aβ plaque burden. It’s worth noting that the attenuated portion of a plaque is the non-compact structure. The level of insulin-degrading enzyme was elevated by both HE-My and HE-Et in cerebral cortex. On the other hand, the number of plaque-activated microglia and astrocytes in cerebral cortex and hippocampus were diminished, the ratio of nerve growth factor (NGF) to NGF precursor (proNGF) was increased and hippocampal neurogenesis was promoted after these administrations. All the mentioned benefits of these administrations may therefore improve the declined activity of daily living skill in APPswe/PS1dE9 transgenic mice.

Conclusions: These results highlight the therapeutic potential of HE-My and HE-Et on Alzheimer’s disease. Therefore, the effective components of HE-My and HE-Et are worth to be developed to become a therapeutic drug for Alzheimer’s disease.

Download this pdf

Cyanthin Diterpenoid and Sesterterpene Constituents of Hericium erinaceus Mycelium Ameliorate Alzheimer’s Disease-Related Pathologies - Tzeng Tsai-Teng, et. al. (22 pages)© (2018) The authors.

Abstract - Hericium erinaceus was used in traditional Chinese medicine for physiologically beneficial medicines. Recently, it has become a candidate in causing positive brain health-related activities.

We previously reported that Hericium erinaceus mycelium ameliorates Alzheimer’s disease (AD)-related pathologies. To reveal the role of the cyanthin diterpenoid and sesterterpene constituents on this effects, erinacine A and S were isolated and their effects on attenuating AD-related pathology in APPswe/PS1dE9 transgenic mice were investigated.

A 30 day short-term administration of erinacine A and S were performed to explore the effect of each erinacine on AD-related pathology including amyloid β production and degradation, plaque formation, plaque growth, glial activation and neurogenesis deterioration.

Our results indicated the benefit effects of both erinacine A and S in cerebrum of APPswe/PS1dE9 mice, including: (1) attenuating cerebral plaque loading by inhibiting plaque growth; (2) diminishing the activation of glial cells; (3) raising the level of insulin degrading enzyme; and (4) promoting hippocampal neurogenesis. Moreover, erinacine A reduced the level of insoluble amyloid β and C-terminal fragment of amyloid precursor protein which was not mediated by erinacine S.

We further performed a long term administration of erinacine A and found that erinacine A recovered the impairment in the tasks including burrowing, nesting, and Morris water maze. Our data pointed out that although both erinacine A and S reduce AD pathology via reducing amyloid deposition and promoting neurogenesis, erinacine A can also inhibit amyloid β production and is worth to be further developed for AD therapeutic use.

Download this pdf

Protective Effect of Ethanol Extracts of Hericium erinaceus on Alloxan-Induced Diabetic Neuropathic Pain in Rats - Tsai-Teng, et. al. (5 pages)© (2015) The authors.

Abstract - We investigated the effects of Hericium erinaceus (HEE) on alloxan induced diabetic neuropathic pain in laboratory rats.

Alloxan induced diabetic rats were administered orally HEE. After 6 weeks of treatments, treatment with HEE 40 mg/kg in diabetic animals showed significant increase in pain threshold and paw withdrawal threshold and significant decrease in serum glucose and urine glucose.

We also observed a significant increase in lactate dehydrogenase (LDH), Lipid peroxidation (LPO), glutathione peroxidase (GPx) activity, glutathione reductase (GR) activity, catalase (CAT) activity, Na+K+ATPase activity, and glutathione S transferase (GST) activity along with significant decreased levels of glutathione (GSH) content in diabetic rats.

The total antioxidant status (TAOS) in the HEE-treated groups was significantly lower than that in the alloxan-treated group. HEE can offer pain relief in diabetic neuropathic pain. The improvement in diabetic state after HEE treatment along with the antioxidant activity could be the probable way by which it had alleviated diabetic neuropathy

Download this pdf

A phase I/II trial of a polysaccharide extract from Grifola frondosa (Maitake mushroom) in breast cancer patients- immunological effects - Gary Deng et.al. - J Cancer Res Clin Oncol. 2009 September; 135(9): 1215–1221 © (2009) The authors.

Abstract
Background — Cancer patients commonly use dietary supplements to “boost immune function”. A polysaccharide extract from Grifola frondosa (Maitake extract) showed immunomodulatory effects in preclinical studies and therefore the potential for clinical use. Whether oral administration in human produces measurable immunologic effects, however, is unknown.
Methods — In a phase I/II dose escalation trial, 34 postmenopausal breast cancer patients, free of disease after initial treatment, were enrolled sequentially in five cohorts. Maitake liquid extract was taken orally at 0.1, 0.5, 1.5, 3, or 5 mg/kg twice daily for 3 weeks. Peripheral blood was collected at days −7, 0 (prior to the first dosing), 7, 14, and 21 for ex vivo analyses. The primary endpoints were safety and tolerability.
Results — No dose-limiting toxicity was encountered. Two patients withdrew prior to completion of the study due to grade I possibly related side effects: nausea and joint swelling in one patient; rash and pruritus in the second. There was a statistically significant association between Maitake and immunologic function (p < 0.0005). Increasing doses of Maitake increased some immunologic parameters and depressed others; the dose–response curves for many endpoints were non- monotonic with intermediate doses having either immune enhancing or immune suppressant effects compared with both high and low doses.
Conclusions — Oral administration of a polysaccharide extract from Maitake mushroom is associated with both immunologically stimulatory and inhibitory measurable effects in peripheral blood. Cancer patients should be made aware of the fact that botanical agents produce more complex effects than assumed, and may depress as well as enhance immune function.

Download this pdf

Anti-diabetic mechanism of Maitake - H. Nanba et.al. - Mushroom Biology and Mushroom products p. 215 - 222 © (1996) The authors.

Abstract
No abstract available

Download this pdf

Can Maitake MD-Fraction Aid Cancer Patients - H. Nanba et.al. - Alternative Medicine Review ◆ Volume 7, Number 3 © (2002) The authors.

Abstract - Maitake mushroom (Grifola frondosa) MD-fraction containing beta-1,6 glucan with beta-1,3 branched chains has previously exhibited strong anticancer activity by increasing immune-competent cell activity.

In this non-random case series, a combination of MD-fraction and whole maitake powder was investigated to determine its effectiveness for 22- to 57-year-old cancer patients in stages II- IV. Cancer regression or significant symptom improvement was observed in 58.3 percent of liver cancer patients, 68.8 percent of breast cancer patients, and 62.5 percent of lung cancer patients.

The trial found a less than 10- 20 percent improvement for leukemia, stomach cancer, and brain cancer patients. Furthermore, when maitake was taken in addition to chemotherapy, immune-competent cell activities were enhanced 1.2-1.4 times, compared with chemotherapy alone. Animal studies have supported the use of maitake MD- fraction for cancer.

Download this pdf

β1,3-GLUCAN ANTICANCER EFFICACIES AND SYNERGIES: A REVIEW - Jennifer Story et.al. - American Journal of Immunology 10 (3): 131-143, 2014 © (2014) The authors.

Abstract - β1,3-glucans from fungi, cereals, seaweeds and bacteria have been shown to possess favourable biological and anti-carcinogenic activities including upregulation of phagocytosis, cytokine production enhancement, superoxide and nitrite production; antibody secretion and stimulation of signalling pathways associated with proto-oncogene expression. However, human dietary supplements containing β1,3-glucans vary in efficacy due to glucan source, the lifecycle stage of the source at extraction, extraction methods, purity, concentration and combination with other immunomodulators.

A review of efficacy of some commercially available β1,3-glucan products is presented. Three apparently efficacious products in which β1,3-glucan was the only immunomodulator were identified: Glucan #300®, Maitake Gold 404® (diluted Yukiguni Maitake MD Fraction®) and Betamune®. A trial of Maitake Gold 404® produced evidence of standardisation problems. It is recommended that Yukiguni Maitake MD Fraction® (a more standardised alternative), Glucan #300® and Betamune® be comparatively trialled at optimal doses across immunological measures and tumor reduction.

β1,3-glucans have been shown to be synergistic with conventional cancer therapies and monoclonal antibodies, as well as immunomodulators including vitamin C, transresveratrol, humic acids and Ashwagandha (Withania somnifera).

Trialled commercially available products containing immunomodulator combinations have been shown to be inefficacious, apart from RVB300®, a β1,3-glucan/transresveratrol/vitamin C combination. The efficacies of various combinations of β1,3-glucans with other immunomodulators and the details of specific β1,3-glucan/monoclonal antibody synergies in treating particular cancer cell lines, require systematic elucidation.

Download this pdf

Immunostimulating properties of two different β-glucans isolated from Maitake mushroom - Vetvicka, et.al. - JANA Vol. 8, No. 3 © (2005) The authors.

Abstract - - Comparison of the commercially available supplements MaitakeGOLD 404® and Maitake D-fraction®. A number of immunological parameters were tested: phagocytosis, NK-cell activity, expression of surface markers, cytokine secretion and apoptosis.

Download this pdf

Oral administration of soluble b-glucans extracted from Grifola frondosa induces systemic antitumor immune response and decreases immunosuppression in tumor-bearing mice - Nanba H, et.al. - Int. J. Cancer: 133, 108–120 © (2013) The authors.

Abstract - Maitake D (MD)-Fraction is a highly purified soluble b-glucan derived from Grifola frondosa (an oriental edible mushroom). Intraperitoneal (i.p.) injection of MD-Fraction has been reported to inhibit tumor growth via enhancement of the host immune system.

In this study, we demonstrated that oral administration of MD-Fraction as well as i.p. injection significantly inhibited tumor growth in murine tumor models. After oral administration, MD-Fraction was not transferred to the blood in its free form but was captured by antigen-presenting cells such as macrophages and dendritic cells (DCs) present in the Peyer’s patch. The captured MD-Fraction was then transported to the spleen, thereby inducing the systemic immune response.

Our study showed that MD-Fraction directly induced DC maturation via a C-type lectin receptor dectin-1 pathway. The therapeutic response of orally administered MD-Fraction was associated with (i) induced systemic tumor-antigen specific T cell response via dectin-1- dependent activation of DCs, (ii) increased infiltration of the activated T cells into the tumor and (iii) decreased number of tumor-caused immunosuppressive cells such as regulatory T cells and myeloid-derived suppressor cells. Our preclinical study suggests that MD-Fraction is a useful oral therapeutic agent in the management of patients with cancer.

Download this pdf

PSP in clinical cancer therapy - A brief overview of Phase I, II and III trials - Prof. Qing-yao Yang - Shanghai Teachers Academy, 2000 © (2000) The author.

Abstract - Polysaccharide-peptide (PSP) is a protein bound polysaccharide isolated from the Cov-1 strain of Yunzhi and made from modern alcohol extraction techniques. Each capsule contains 0.34 grams of PSP. Experimental in-vitro and in-vivo studies have shown PSP inhibits the proliferation of cancer cells including P338 leukemia cells, S 180 cells, Ehrlich ascites, and stomach and lung cancer cells. It also inhibits the growth of some tumors such as the lymphatic tumor of human skin tissue cells. In addition, PSP affects the immune system of mice by stimulating the production of α-interferons, increasing the phagocytic index and metabolic rate of the reticuloendothilial system and by raising the HC 50 (median hemolytic dose), IgG and PFC (plaque forming cell) values. Human in-vivo experiments have also shown PSP can modulate the immune system by helping to prevent and partly eliminate the side effects of radiation and chemotherapeutic agents used by cancer patients.

Download this pdf

The Use of Mushroom Glucans and Proteoglycans in Cancer Treatment - Parris M. Kidd, PhD -

Abstract - Immunoceuticals can be considered as substances having immunotherapeutic efficacy when taken orally. More than 50 mushroom species have yielded potential immunoceuticals that exhibit anticancer activity in vitro or in animal models and of these, six have been investigated in human cancers. All are non-toxic and very well tolerated. Lentinan and schizophyllan have little oral activity. Active Hexose Correlated Compound (AHCC) is poorly defined but has shown early clinical promise. Maitake D- Fraction has limited proof of clinical efficacy to date, but controlled research is underway. Two proteoglycans from Coriolus versicolor – PSK (Polysaccharide-K) and PSP (Polysaccharide-Peptide) – have demonstrated the most promise. In Japanese trials since 1970, PSK significantly extended survival at five years or beyond in cancers of the stomach, colon-rectum, esophagus, nasopharynx, and lung (non-small cell types), and in a HLA B40-positive breast cancer subset. PSP was subjected to Phase II and Phase III trials in China. In double-blind trials, PSP significantly extended five-year survival in esophageal cancer. PSP significantly improved quality of life, provided substantial pain relief, and enhanced immune status in 70-97 percent of patients with cancers of the stomach, esophagus, lung, ovary, and cervix. PSK and PSP boosted immune cell production, ameliorated chemotherapy symptoms, and enhanced tumor infiltration by dendritic and cytotoxic T-cells. Their extremely high tolerability, proven benefits to survival and quality of life, and compatibility with chemotherapy and radiation therapy makes them well suited for cancer management regimens.

Download this pdf

Chemopreventive Effect of PSP Through Targeting of Prostate Cancer Stem Cell-Like Population - Sze-Ue Luk et. al. - PLoS ONE May 2011 ◆ Volume6, Number5 ◆ 2011 ©2011 the authors.

Abstract - Recent evidence suggested that prostate cancer stem/progenitor cells (CSC) are responsible for cancer initiation as well as disease progression. Unfortunately, conventional therapies are only effective in targeting the more differentiated cancer cells and spare the CSCs. Here, we report that PSP, an active component extracted from the mushroom Turkey tail (also known as Coriolus versicolor), is effective in targeting prostate CSCs. We found that 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. Meanwhile, PSP treatment not only suppressed the ability of PC-3 cells to form prostaspheres under non-adherent culture conditions, but also inhibited their tumorigenicity in vivo, further proving that PSP can suppress prostate CSC properties. To investigate if the anti-CSC effect of PSP may lead to prostate cancer chemoprevention, transgenic mice (TgMAP) that spontaneously develop prostate tumors were orally fed with PSP for 20 weeks. Whereas 100% of the mice that fed with water only developed prostate tumors at the end of experiment, no tumors could be found in any of the mice fed with PSP, suggesting that PSP treatment can completely inhibit prostate tumor formation. Our results not only demonstrated the intriguing anti-CSC effect of PSP, but also revealed, for the first time, the surprising chemopreventive property of oral PSP consumption against prostate cancer.

Download this pdf

Clinical Implications of PSP in Oncology - T.F. Liu and W.C. Xue - Department of Radiation Oncology Cancer Hospital, Shanghai Medical University ◆ (1989) © the authors.

Abstract - Up to now, the three main weapons against cancer have been surgery, radiotherapy and chemotherapy. Although these classical methods of treatment have given fairly good results in general, the results have yet to be improved, especially in late cases. Thus for many years, the search for a more effective means of anti-cancer treatment has been going on world-wide. An ideal drug would of course be one that could directly kill all the cancer cells without harming the normal tissues, and also without causing general toxicity. However, at present a more practical approach is to use drugs that would either enhance the biological effects of radiation or of cytotoxic agents, or strengthen the organism's immunological defenses. In recent years, several such drugs have been undergoing clinical trials, for example, Misonidazole, RS 2508, OK-432, PSK, etc. The drug that we shall talk about today is polysaccharide peptide, hereafter referred to as PSP.

Download this pdf

Coriolus versicolor - Detailed Scientific Review - MD Anderson Cancer center University of Texas © University of Texas

Abstract - Coriolus versicolor was first recorded during the Ming Dynasty of China, and subsequently in a 1965 Japanese report of a patient with stomach cancer who benefited from drinking a tea, Saru-no-koshikake, that contained this mushroom. Subsequent laboratory and animal research identified the source of the tea's anti-tumor effects to be two polysaccharides. In 1989, two investigators at the U. S. National Cancer Institute (Jong and Donovick) published a review of antitumor and antiviral substances from fungi including Coriolus versicolor. This review noted seven studies and two U. S. patents issued for polysaccharides extracted from Coriolus versicolor. One extract was a polysaccharide-protein (proteoglycan) known as polysaccharide Kurcha (PSK or Krestin), and it had been found to be effective in the treatment of Ehrlich carcinoma and sarcoma 180 tumors in mice. Furthermore, PSK had not exhibited any of the cytotoxicity or other side effects commonly seen with conventional anticancer treatment. Subsequent laboratory and animal studies have further defined the antitumor, antimicrobial, antiviral and immune enhancing properties in both PSK and another protein-bound polysaccharide known as polysaccharide-protein complex (PSPC or PSP). Both substances are extracted by hot water from the mushroom's cultured mycelium.

Download this pdf

General review of polysaccharopeptides (PSP) from C. versicolor: Pharmacological and clinical studies - Cancer Therapy Vol 6, 117-130, 2008 ©2008 the authors

Abstract - In China, C. versicolor is named Yun Zhi (meaning "cloud-like mushroom"). C. versicolor is mainly used as an adjuvant in the treatment of cancer. The active principle derived from C. versicolor belongs to a new class of elements called biological response modifiers (BRM) which are defined as agents capable of stimulating the immune system and thereby, they express various therapeutic effects. The best know commercial polysaccharopeptide preparations of C. versicolor are polysaccharopeptide Krestin (PSK) and polysaccharopeptide (PSP). One of the most important functions of PSP and PSK is their immunomodulatory and anti-cancer actions. The present paper reviewed and summarized the pharmacological and clinical properties, as well as its background of Coriolus versicolor or PSP.

Download this pdf

Oral coriolus versicolor polysaccharide peptide is beneficial by slowing the progression of lung cancer - Ip, S; Lam, CL et.al. - HongKong Medical Journal Vol 9 No 1 February 2003 © 2003 the authors

Abstract - Our preliminary data show that PSP treatment could be associated with slower deterioration in the clinical course of patients with advanced Non Small Cell Lung Cancer, and have no adverse reactions. Our results not only suggest that further clinical trials should be conducted on the effects of PSP on NSCLC, but also show that standard GCP trial criteria could be applicable to research in alternative medicine.

Download this pdf

Polysaccharopeptides of Coriolus versicolor: physiological activity, uses, and production - Jian Cui, Yusuf Chisti - Biotechnology Advances 21 (2003) 109–122 © 2003 Elsevier Science Inc.

Abstract - The protein-bound polysaccharides or polysaccharopeptides produced by Coriolus versicolor are effective immunopotentiators, which are used to supplement the chemotherapy and radiotherapy of cancers and various infectious diseases. Antitumor activity of polysaccharopeptides has been documented. Several kinds of protein-bound polysaccharides have been shown to be produced by the white rot fungus, C. versicolor. Although some of these polymers are structurally distinct, they are not distinguishable in terms of their physiological activity. This review focuses on the physiologically active polysaccharopeptides of C. versicolor. In nature, C. versicolor occurs as a mushroom body, but the fungus can be grown as mycelial biomass in submerged culture in bioreactors. Mushrooms gathered in the wild, cultivated mushrooms, and the mycelial biomass of submerged culture are used to produce the polysaccharopeptides. Submerged cultures are typically carried out in batches lasting 5–7 days and at 25–27 jC. Hot water extraction of the biomass is used to recover the thermostable polysaccharopeptides that are concentrated, purified, and dried into a powder for medicinal use. In view of the documented physiological benefits of these compounds, extensive research is underway on the structure, composition, production methods, and use of new C. versicolor strains for producing the therapeutic biopolymers. Properties, physiological activity, recovery, and purification of the bioactive polysaccharopeptides are discussed.

Download this pdf

Ganoderma - A therapeutic fungal biofactory - R. Russell M. Paterson et.al. - Phytochemistry 67 (2006) 1985 - 2001 © (2006) The authors.

Abstract - Ganoderma is a basidiomycete white rot fungus which has been used for medicinal purposes for centuries particularly in China, Japan and Korea. A great deal of work has been carried out on Ganoderma lucidum. The common names for preparations include Lingzhi, Munnertake, Sachitake, Reishi and Youngzhi. This review collates the publications detailing activities and compounds by representative species whilst considering the most valid claims of effectiveness. The biological activities reported of preparations from Ganoderma are remarkable and given most emphasis herein as distinct from structure/activity information. The metabolites consist of mainly polysaccharides and terpenoids. Many are activities against the major diseases of our time and so the present review is of great importance. The list of effects is huge ranging from anti-cancer to relieving blockages of the bladder. However, the reports have not all been tested scientifically with the convincing evidence reserved for assays of pure compounds. It is a prime example of an ancient remedy being of great relevance to the modern era. There does appear to be an assumption that the therapeutic effects attributed to the fungus have been proven. The next step is to produce some effective medicines which may be hampered by problems of mass production.

Download this pdf

Reishi or Ling Zhi (Ganoderma lucidum) - Solomon P. Wasser - Encyclopedia of Dietary Supplements: 603-622 © (2005) Marcel Dekker.

Abstract - Extensive review of Reishi's properties and scientific research, up to 2005.

Download this pdf

Ganoderma lucidum (Lingzhi or Reishi) A Medicinal Mushroom - Sissi Wachtel-Galor et. al. - Herbal Medicine: Biomolecular and Clinical Aspects. 2nd edition. Boca Raton (FL): CRC Press; 2011: Chapter 9 © (2011) The authors.

Abstract - In Chinese, the name lingzhi represents a combination of spiritual potency and essence of immortality, and is regarded as the “herb of spiritual potency”, symbolizing success, well-being, divine power, and longevity. Among cultivated mushrooms, G. lucidum is unique in that its pharmaceutical rather than nutritional value is paramount. A variety of commercial G. lucidum products are available in various forms, such as powders, dietary supplements, and tea. These are produced from different parts of the mushroom, including mycelia, spores, and fruit body. The specific applications and attributed health benefits of lingzhi include control of blood glucose levels, modulation of the immune system, hepatoprotection, bacteriostasis, and more. The various beliefs regarding the health benefits of G. lucidum are based largely on anecdotal evidence, traditional use, and cultural mores. However, recent reports provide scientific support to some of the ancient claims of the health benefits of lingzhi.

Download this pdf

Biologically active metabolites of the genus Ganoderma - 3 decades of myco-chemistry research - Angel Trigos et. al. - Revista Mexicana de micologia 34 © (2011) The authors.

Abstract - The fungi belonging to the genus Ganoderma have been used since ancient times in Eastern traditional medicine in the treatment and prevention of several diseases such as cancer, hypertension and diabetes, among many other conditions. More than 140 biologically active triterpenoids and 200 polysaccharides, as well as proteins and miscellaneous metabolites have been isolated from the fruiting bodies, mycelium and spores of different species of Ganoderma. The aim of this study is to summarize the main biologically active metabolites isolated from members of this genus to date, yet without pretending to be an exhaustive review, since that would be impossible due the dynamism of the field.

Download this pdf

Effect of thirty days supplementation of standardized LingZhi extract on aerobic, anaerobic and strength parameters in trained athletes - Abdul Rashid Aziz, et.al. - International Journal of Applied Sports Sciences 2006, Vol. 18, no.1: 8-21 © (2006) The authors.

Abstract - One of the reputed effects, albeit still unproven, is Reishi's ability to improve human physical performance. This study is assessing the potential ergogenic effects on exercise performance.

Download this pdf

Ganoderma lucidum (‘Lingzhi’), a Chinese medicinal mushroom: biomarker responses in a controlled human supplementation study - Sissi Wachtel-Galor, et.al. - British Journal of Nutrition (2004), 91, 263–269 ¬© (2004) The authors.

Abstract - Lingzhi (Ganoderma lucidum) is a woody mushroom highly regarded in traditional medicine and is widely consumed in the belief that it promotes health and longevity, lowers the risk of cancer and heart disease and boosts the immune system. However, objective scientific validation of the putative health benefits of Lingzhi in human subjects is lacking, and issues of possible toxicity must be addressed. The present double-blinded, placebo-controlled, cross-over intervention study investigated the effects of 4 weeks Lingzhi supplementation on a range of biomarkers for antioxidant status, CHD risk, DNA damage, immune status, and inflammation, as well as markers of liver and renal toxicity. It was performed as a follow-up to a study that showed that antioxidant power in plasma increased after Lingzhi ingestion, and that 10 d supplementation was associated with a trend towards an improved CHD biomarker profile. In the present study, fasting blood and urine from healthy, consenting adults (n 18; aged 22–52 years) was collected before and after 4 weeks supplementation with a com- mercially available encapsulated Lingzhi preparation (1·44 g Lingzhi/d; equivalent to 13·2 g fresh mushroom/d) or placebo. No significant change in any of the variables was found, although a slight trend toward lower lipids was again seen, and antioxidant capacity in urine increased. The results showed no evidence of liver, renal or DNA toxicity with Lingzhi intake, and this is reassuring. The present study of the effects in healthy, well-nourished subjects provides useful, new scientific data that will support controlled intervention trials using at- risk subjects in order to assess the therapeutic effect of Lingzhi in the promotion of healthy ageing.

Download this pdf

Cat Allergy Alleviated with Reishi - Howell Lewis - Positive Health © (2005) The author.

Abstract - Case study.

Download this pdf

Reishi Mushroom as a Hayfever Remedy - Dale Pinnock - Positive Health © (September 2007) The author.

Abstract - Case study.

Download this pdf

Medical preparations based on Mumijo - Yarovaya, Sofiya Alekseevna - Voronezh State Medical Academy. Department of Pharmacognosia and Pharmaceutical Commodities © (2007) The author.

Abstract - Mumijo is not a panacea for all deceases. Nevertheless, modern science has clearly shown that mumijo has a broad spectrum of biological action: anti-bacterial, bacteriostatic, anti-inflammatory, choleric, tonic and anti-stress. Due to its composition mumijo stimulates the activity of many enzyme systems of the body and supports a variety of immunological processes.

This 19-page article (in Russian) is available for free download in PDF format (zipped, 219 KB)