Medicinal Mushrooms  For OPTIMUM HEALTH AND LONGEVITY

 Ken Babal, C.N.

We all know that vitamin and mineral supplements can augment diets by providing essential nutrients that ward off disease. Likewise, botanicals can help us stay well, and can be used medicinally. There is yet a third category that ranks high for cultivating optimum health and resistance to disease. This is the mushroom category. Mushrooms are members of the fungal family, sometimes referred to as the third kingdom. Being neither plant nor animal, they possess highly unique characteristics that confer a wide array of health benefits.

In addition to essential nutrients, mushrooms contain many compounds with protective and therapeutic actions. Of particular interest is beta glucan, a complex carbohydrate, or polysaccharide that activates cellular immunity. Although we generally think of carbohydrates as providing energy, research reveals that some are involved in molecular recognition and cellular communication. Beta glucans are found in other foods, including oats and yeast. However, their chemical structures and effects are different from those of the beta glucans in mushrooms.

For thousands of years, mushrooms have been revered in China and Japan for their ability to maintain and improve health, preserve youth, and increase longevity. In many classic herbal formulations they are considered the main ingredient, or emperor. Today, there are hundreds of scientific studies validating the traditional usage of mushrooms. In numerous experiments and clinical trials, mushrooms have demonstrated antiallergenic, antibacterial, anti-inflammatory and antiviral actions, and an ability to sensitize cells to insulin.

There are a number of active ingredients in mushrooms that are obtained by alcohol extraction or methods other than simple hot water extraction.

The following are some examples of proven medicinal mushroom standardized extracts.

D-Fraction from Maitake  is perhaps the most famous of the mushroom extracts, having been the focus of much anticancer research. D-Fraction is a concentrated extract containing a protein-bound beta glucan, which has been shown to stimulate vital components of cellular immunity such as T cells, B cells, macrophages and natural killer (NK) cells.¹ Last year, a breakthrough study found that D-Fraction up-regulates twenty-two apoptosis genes, including the BAK-1 gene.² Researchers concluded that D-fraction has strong anti-cancer properties in breast cancer cells through BAK-1 gene expression. This is highly significant because it places D-fraction in a unique category apart from ordinary “immune boosters,” antioxidants and apoptosis-inducers.

Maitake is also the source of a unique glycoprotein called SX-Fraction, which has been shown to enhance insulin sensitivity. SX-Fraction is a completely different compound from D-Fraction, and was awarded a US patent in 2007 for anti-diabetic, anti-hypertensive, anti-obesity and anti-hyperlipidemic effects.³ Studies at Georgetown University found that SX-Fraction reduced levels of fasting blood glucose, blood pressure and body weight in genetically obese and diabetic rats. The extract also prevented hypertensive rats on a high sugar diet from developing insulin resistance. Furthermore, a clinical study found that Type 2 diabetics taking SX-Fraction for two months were able to significantly reduce their fasting blood glucose, triglycerides, insulin and body weight.⁴

Reishi is perhaps the most renowned of all medicinal mushrooms, and is prescribed as an anti-aging tonic. It is said to be a supreme “shen” (spiritual) tonic that invokes peacefulness and changes how we perceive life. Reishi is widely used in Asia to support cardiovascular functions and reduce LDL cholesterol. It has been found to be effective in preventing and treating arteriosclerosis, angina and shortness of breath associated with coronary heart disease.

Reishi contains steroid-like compounds (triterpenes) that inhibit inflammation and histamine, the chemical responsible for allergic symptoms. Medicinal triterpenes are fat-soluble and are concentrated by alcohol extraction.

Lion’s Mane is one of the edible mushrooms widely distributed in Japan and China.  Studies show that a class of compounds in Lion’s Mane, called hericenones, is able to regenerate neurons by stimulating production of Nerve Growth Factor.⁵ In addition, a fat-soluble fraction isolated from Lion’s Mane, called amyloban, is able to protect against neuronal cell death caused by toxic beta amyloid peptide, the main component of plaque that develops in the brains of Alzheimer’s disease patients.⁶

A study at a Chinese Pharmaceutical University compared Lion’s Mane extract with donepezil (Aricept), a common Alzheimer’s drug.⁷ Results showed that rats treated with the extract performed a water maze test equal to or better than those receiving the drug, depending on the dosage of the extract. Also, a double-blind, placebo-controlled study, demonstrated that Lion’s Mane is effective in patients diagnosed with mild cognitive impairment.⁸

And others mushrooms extracts are Agaricus, Cordyceps, Shiitake, Tremella, Meshima, Chaga, Coriolus and Poria. Agaricus enjoys superstar status in Japan. Its medicinal actions include counteracting or preventing tumors, fighting viruses, lowering cholesterol, regulating blood sugar levels and enhancing immunity. Cordyceps strengthens lung power and is a good choice for those who require energy for physical work or sports. It is considered one of the best sexual tonic. Shiitake is the most researched mushroom in the world, and is the source of two extensively studied derivatives used in Japan: lentinan and LEM. Tremella is a mushroom whose skin hydrating properties make it particularly useful as a beauty aid, both internally and externally. When compared to a form of hyaluronic acid, it demonstrated a stronger water holding capacity (500 hundred times its weight). Meshima mushroom has been attracting attention as being particularly protective of breast tissue. Researchers from Indiana University found that an extract of Meshima suppresses growth and invasive behavior of breast cancer cells.⁹ Chaga has received wide acclaim as a medicinal mushroom mentioned in the 1968 novel Cancer Ward. In Russian medicine, a tea made from Chaga is used as to treat ulcers and tuberculosis, and to counteract or prevent tumors. The immune-enhancing activities of Coriolus and its constituents have been extensively studied in Japan since the mid-1970s, with over 400 clinical studies conducted on it. It is the source of PSK (polysaccharide-K) (brand name Krestin), one of the all-time best-selling cancer drugs sold mainly in Europe and Japan. Poria is very popular in traditional Chinese formulations for tonifying the spleen and kidney and for clearing dampness.

References

1. Kodama, N. et al. “Effect of Maitake (Grifola frondosa) D-Fraction on the Activation of NK Cells in Cancer Patients,”  Journal of Medicinal Food 6 (4) 2003, pp. 371-377.

2. Soares, R. et al. “Maitake (D-Fraction) Mushroom Extract Induces Apoptosis in Breast Cancer Cells by BAK- 1 Gene Activation,” Journal of Medicinal Food XX(X) 2011, pp. 1-10.

3. US Patent No. 7,214,778 for “Glycoprotein with Anti-diabetic, Anti-hypertensive, Anti-obesity and Anti-hyperlipidemic Effects from Grifola Frondosa, and a Method for Preparing Same.” (2007)

4. Konno, S. et al “A possible hypoglycemic effect of maitake mushroom on type 2 diabetic patients.” Diabetic Med. 18, 2001.

5. Kawagishi, H and Zhuang, C. “Compounds for dementia from Hericium erinaceum.” Drugs of the Future, 2008, 33(2): 149-155.

6. Nagai, K. et al “Dilinoleoyl-phosphatidylethanolamine from Hericium erinaceum protects against ER stress-induced Neuro2a cell death via protein kinase C pathway.” J Nutr Biochem, 17 (2006) 525-530.

7. Kawagishi, H et al “Anti-dementia effects of a low polarity fraction extracted from Hericium erinaceum.” Abstracts of the 5^th  International Medicinal Mushroom Conference, p. 18-19, September 5^th – 8^th, 2009, Nantong, China.

8. Mori, K et al “Improving Effects of the Mushroom Yamabushitake (Hericium erinaceum) on Mild Cognitive Impairment: A Double-blind Placebo-controlled Clinical Trial.” Phytother Res, 23, 367-372 (2009).

9. Sliva D. et al “Phellinus Linteus Suppresses Growth, Angiogenesis, and Invasive Behavior of Breast Cancer Cells Through the Inhibition of AKT Signaling” British Journal of Cancer, 2008, pp. 1348-56.

Shiitake Mushrooms (Lentinus edodes)

Shiitake mushroom (Lentinus edodes), very popular worldwide as an edible mushroom, has history of artificial cultivation dating as far back as the Ming Dynasty (1368-1644) in China. Lentinan, derived from fruit body of Shiitake, is one of the three mushroom origin anti-cancer drugs approved by the Ministry of Health, Labor and Welfare in Japan. Lentinan exhibits strong immune responses and has been extensively studied in association with cancers and viral infections. Shiitake contains a variety of constituents that have demonstrated a range of actions, including immune modulation, anti-tumor, liver protecting, cholesterol lowering, anti-viral and blood pressure lowering. Shiitake extract is also a potent anti-fungal agent, effective against candida albicans.

Bioactive constituents:
Beta-glucan, Heteroglucan, Adenine delivative, Guanosine 5′-monophosphate, polyacelylene

Bioactivities:
• Anti-tumor: Enhances immune functions / Activates macrophage, T-cell and NK-cell / Increases production of TNF-α, interleukins, interferon
• Anti-HIV: Synergistic effect with azidothymidine (AZT)
• Anti-hyperlipemia: Promotes the metabolism and excretion of cholesterol
• Anti-thrombogenicity: Inhibits platelet aggregation
• Natural antidote: Strengthens the livers function of detoxification

References:
(1) G. Chihara et al, Nature, 222:687 (1969)
(2) I. Chibata et al, Experientia, 25:1237 (1969)
(3) T. Kamiya et al, Tetrahedron Lett., 53:4279 (1969)
(4) G. Chihara et al, Cancer Res., 30:2776 (1970)
M. Hayakawa et al, Nippon Rohnenigakukai Zashi (Japanese), 22:477 (1971)
(6) T. Sasaki et al, Carbohydr. Res., 47:99 (1976)
(7) Y. Deslandes et al, Macromolecules, 13:1466 (1980)
(8) J. Hamuro, Marcel Dekker, New York, p. 409 (1984)
(9) S. Mohri et al, Biryo Eiyohso Kenkyu, 3:49 (1986)
(10) T. Tochikura et al, Jpn. J. Cancer Res., 78:583 (1987)
(11) G. Chihara, Chemistry and Biochemistry of Mushrooms (Japanese), Gakkaishuppan Center, p. 323 (1992)
(12) T. Mizuno, Food Reviews International, 11(1):111 (1995)
(13) K. Minato et al, International Journal Medicinal Mushrooms, 1(3):243 (1999)

Ayano ITOH, ^a  Katsuhiro ISODA, ^a  Masuo KONDOH, ^a  Malaya KAWASE, ^a  Akihiro WATARI, ^a Masakazu KOBAYASHI,^b Makoto TAMESADA,^b and Kiyohito YAGI * ‘^a

^a Graduate School of Pharmaceutical Sciences, Osaka University; 1-6 Yamada-oka, Saha, Osaka 565-0871, Japan: and ^b Research and Development Center, Kobayashi Pharmaceutical Co., Ltd.; 1-30-3 Toyokawa, Ibaraki, Osaka 567-0057, Japan. Received December 22, 2009; accepted March 16, 2010; published online March 19, 2010

The mycelia of the edible mushroom Lentinula edodes ( shiitake ) can be cultured in solid medium containing lignin, and the hot-water extracts (L.E.M.) is commercially available as a nutritional supplement. During the cultiva­tion, phenolic compounds, such as syringic acid and vanillic acid, were produced by lignin-degrading peroxidase secreted from L. edodes mycelia. Since these compounds have radical scavenging activity, we examined their pro­tective effect on oxidative stress in mice with CCI₄-induced liver injury. We examined the hepatoprotective effect of syringic acid and vanillic acid on CCI₄-induced chronic liver injury in mice. The injection of CCI₄ into the peritoneal cavity caused an increase in the serum aspartate aminotransferase (AST) and alanine aminotrans­ferase (ALT) levels. The intravenous administration of syringic acid and vanillic acid significantly decreased the levels of the transaminases. Four weeks of CCI₄ treatment caused a sufficiently excessive deposition of collagen fibrils. An examination of Azan-stained liver sections revealed that syringic acid and vanillic acid obviously sup­pressed collagen accumulation and significantly decreased the hepatic hydroxyproline content, which is the quan­titative marker of fibrosis. Both of these compounds inhibited the activation of cultured hepatic stellate cells, which play a central role in liver fibrogenesis, and maintained hepatocyte viability. These data suggest that the administration of syringic acid and vanillic acid could suppress hepatic fibrosis in chronic liver injury.

Keith R Martin

Abstract

Background: Cardiovascular disease (CVD) is a leading cause of mortality in the United States as well as globally. Epidemiological studies show that regular fruit and vegetable consumption reduces CVD risk, in part, due to antioxidant activity and immunomodulation since oxidative stress and inflammation are features of atherogenesis. Accumulating evidence also shows that dietary fungi, viz., mushrooms, can protect against chronic disease by altering inflammatory environments such as those associated with CVD although most research has focused on specialty mushrooms. In this study, we tested the ability of both common and specialty mushrooms to inhibit cellular processes associated with CVD.

Methods: Human aortic endothelial cells (HAEC) were incubated overnight with control media with dimethylsulfoxide (DMSO) vehicle (1% v/v) or containing DMSO extracts of whole dehydrated mushrooms (0.1 mg/ mL), which included Agaricus bisporus (white button and crimini), Lentinula edodes (shiitake), Pleurotus ostreatus (oyster), and Grifola frondosa ( maitake ). Monolayers were subsequently washed and incubated with medium alone or containing the pro-inflammatory cytokine IL-1 (5 ng/mL) for 6 h to upregulate pro-atherosclerotic adhesion molecules (AM). AM expression was assayed by ELISA and binding of U937 human monocytes pre-loaded with fluorescent dye was determined.

Results: White button mushrooms consistently reduced (p < 0.05) VCAM-1, ICAM-1, and E-selectin-1 expression, whereas other test mushrooms significantly modulated AM expression singly, collectively, or combinatorially. All mushrooms, however, significantly reduced binding of monocytes to both quiescent and cytokine-stimulated monolayers.

Conclusion: These data provide evidence that dietary mushrooms can inhibit cellular processes such as adhesion molecule expression and ultimate binding of monocytes to the endothelium under pro-inflammatory conditions, which are associated with CVD. As a result, these findings support the notion that dietary mushrooms can be protective against CVD.

J. VETTER*

Department of Botany, Faculty of Veterinary Science, Szent István University, Hungary

The edible mushrooms have different valuable chemical properties (proteins, minerals, aromatic compounds, low lipid and energy contents, etc.) but there are practically no data about the iodine content. The aim of this work was to produce new data on the iodine content of the common edible mushrooms. The inorganic iodine contents of different wild growing (n=49) and cultivated (n=30) mushroom samples were analysed. A partly modified spectrophotometric method was used for the iodine determination in triplicate. The average iodine contents of the wild growing and the cultivated species and samples were 284 (±211) and 148 (±86) μg kg^–1 d.m., respectively; these data do not differ significantly. The type of nutrition for the mushrooms seems to be the most important factor affecting the iodine level. The lowest values were identified in edible, wood decaying mushrooms. The analysed cultivated taxa (varieties of Agaricus bisporus, Pleurotus ostreatus and Lentinula edodes) do not have significantly different iodine level, however, significantly lower iodine contents were found in mushroom samples produced in Germany than in samples cultivated in Hungary. The inorganic iodine level of edible (wild growing and cultivated) mushrooms is low. The lowest concentrations were identified in the wood-decaying species compared to the mycorrhizal ones. The calculated daily iodine intake of humans by mushrooms only accounts for 4–5% of the daily requirement.

Ayano ITOH, Katsuhiro ISODA, Masuo KONDOH,  Masaya KAWASE, Masakazu KOBAYASHI, Makoto TAMESADA, and Kiyohito YAGI

The edible mushroom Lentinula edodes (shiitake) contains many bioactive compounds. In the present study, we cultivated L. edodes mycelia ( Shiitake ) in solid medium and examined the hot-water extract (L.E.M.) for its suppressive effect on concanavalin A (ConA)-induced liver injury in mice. ConA injection into the tail vein caused a great in­crease in the serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels. The intraperi­toneal administration of L.E.M. significantly decreased the levels of the transaminases. L.E.M. contains many bioactive substances, including polysaccharides and glucan, which could be immunomodulators. Since ConA-in­duced liver injury is caused by the activation of T cells, immunomodulating substances might be responsible for the suppressive effect of L.E.M. L.E.M. also contains phenolic compounds that are produced from lignocellulose by mycelia-derived enzymes. The major phenolics in L.E.M., syringic acid and vanillic acid, were intraperi­toneally injected into mice shortly before the ConA treatment. Similar to L.E.M., the administration of syringic acid or vanillic acid significantly decreased the transaminase activity and suppressed the disorganization of the hepatic sinusoids. In addition, the inflammatory cytokines tumor necrosis factor (TNF)-α, interferon (IFN)-γ, and interleukin (IL)-6 in the serum increased rapidly, within 3 h of the ConA administration, but the administra­tion of syringic acid or vanillic acid significantly suppressed the cytokine levels. Together, these findings indicate that the phenolic compounds in L.E.M. are hepatoprotective through their suppression of immune-mediated liver inflammation.

Sanhong Yu¹, Veronika Weaver¹, Keith Martin² and Margherita T Cantorna*¹

¹Center for Immunology and Infectious Disease, Department of Veterinary and Biomedical Science, The Pennsylvania State University, USA and ²Department of Nutrition, Arizona State University, USA

Abstract

Background: Consumption of edible mushrooms has been suggested to improve health. A number of isolated mushroom constituents have been shown to modulate immunity. Five commonly consumed edible mushrooms were tested to determine whether whole mushrooms stimulate the immune system in vitro and in vivo.

Results: The white button (WB) extracts readily stimulated macrophage production of TNF-α. The crimini, maitake, oyster and shiitake extracts also stimulated TNF-α production in macrophage but the levels were lower than from WB stimulation. Primary cultures of murine macrophage and ovalbumin (OVA) specific T cells showed that whole mushroom extracts alone had no effect on cytokine production but co-stimulation with either lipopolysacharide or OVA (respectively) induced TNF-α, IFN-γ, and IL-1β while decreasing IL-10. Feeding mice diets that contained 2% WB mushrooms for 4 weeks had no effect on the ex vivo immune responsiveness or associated toxicity (changes in weight or pathology of liver, kidney and gastrointestinal tract). Dextran sodium sulfate (DSS) stimulation of mice that were fed 1% WB mushrooms were protected from DSS induced weight loss. In addition, 2% WB feeding protected the mice from transient DSS induced colonic injury. The TNF-α response in the colon and serum of the DSS challenged and 2% WB fed mice was higher than controls.

Conclusion: The data support a model whereby edible mushrooms regulate immunity in vitro. The in vivo effects of edible mushrooms required a challenge with DSS to detect small changes in TNF-α and transient protection from colonic injury. There are modest effects of in vivo consumption of edible mushrooms on induced inflammatory responses. The result is not surprising since it would certainly be harmful to strongly induce or suppress immune function following ingestion of a commonly consumed food.

Edneia A. Souza-Paccola‘; Cleide A. Bomfeti²; Léia C.L. Fávaro²; Inês C.B. Fonseca‘; Luzia D. Paccola-Meirelles²*

¹Departamento de Ciências Agrárias, Universidade Estadual de Londrina, Londrina, PR, Brasil

²Departamento de Ciências Biológicas, Universidade Estadual de Londrina,Londrina, PR, Brasil

ABSTRACT

The antimutagenic effect of the mushrooms Lentinula edodes ( Shiitake ) and Agaricus blazei was studied on conidia of Aspergillus nidulans when exposed to short wave ultraviolet light. Two strains of A. nidulans were used. For the preparation of the extracts, the fresh mushrooms were left in aqueous infusion for 12 hours and heated in a water bath for 15 min at 100ºC, and then the material was filtered. The dehydrated mushrooms were left in aqueous infusion for 12 hours and to filtrated. Both filtrates were used as extracts. A. nidulans conidia were incubated for three hours in water and in mushroom extracts and only after were exposed to UV light (pre­treatment). A. nidulans conidia were suspended in water and in mushroom extracts and immediately submitted to UV light (post-treatment). Conidial suspension in water and in mushroom extracts but without exposure to the mutagenic agent were used as controls. After mutagenic treatment, it was observed an increase in the survival rate of the A. nidulans and a decrease in the percentage of morphologic mutants on conidia treated with mushroom extracts. Our results demonstrated the radioprotective and antimutagenic effect of L. edodes and A. blazei mushrooms on eukaryotic cells when exposed to UV radiation.

Edneia A. Souza-Paccola’; Cleide A. Bomfeti²; Léia C.L. Fávaro²; Inês C.B. Fonseca’; Luzia D. Paccola-Meirelles²*

¹Departamento de Ciências Agrárias, Universidade Estadual de Londrina, Londrina, PR, Brasil; ²Departamento de Ciências Biológicas, Universidade Estadual de Londrina, Londrina, PR, Brasil

ABSTRACT

The antimutagenic effect of the mushrooms Lentinula edodes and Agaricus blazei was studied on conidia of Aspergillus nidulans when exposed to short wave ultraviolet light. Two strains of A. nidulans were used. For the preparation of the extracts, the fresh mushrooms were left in aqueous infusion for 12 hours and heated in a water bath for 15 min at 100ºC, and then the material was filtered. The dehydrated mushrooms were left in aqueous infusion for 12 hours and to filtrated. Both filtrates were used as extracts. A. nidulans conidia were incubated for three hours in water and in mushroom extracts and only after were exposed to UV light (pre­treatment). A. nidulans conidia were suspended in water and in mushroom extracts and immediately submitted to UV light (post-treatment). Conidial suspension in water and in mushroom extracts but without exposure to the mutagenic agent were used as controls. After mutagenic treatment, it was observed an increase in the survival rate of the A. nidulans and a decrease in the percentage of morphologic mutants on conidia treated with mushroom extracts. Our results demonstrated the radioprotective and antimutagenic effect of L. edodes and A. blazei mushrooms on eukaryotic cells when exposed to UV radiation.