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General Chemistry of Medicinal Mushrooms

The mushrooms are a class of fungi which possesses a wide variety of functional chemistry.  Fungi live via an extra cellular life process.  The mushrooms exude protein catalysts which digest the foods around it.  The digestion is then transported back into the fungal cell for use.  Because of this feeding method, mushrooms possess a large amount of Enzymes.(8-12)
The mushroom’s cellular structure is composed of  hundreds of very specific types of complex sugars, called beta-glucans.  Along with these long chain sugars, the mushrooms also produce glycol-proteins.  Sugar structures attached to a protein stem.    

Enzymes, beta glucans and glycol-proteins all have very specific shapes which  interact with structures that are on the cells membrane.  These “sensors / receptors” on the inside and outside of the  cells couple with the mushrooms chemistry and cause the body’s cell to produce a multitude of proteins. In some studies it shows that when cancer cells consume this chemistry from a turkey tail specie that the cancer cell produced new proteins that cause the cancer cells apoptosis in several European studies.

Each protein reacting with the next, like a relay race with many runners involved.  This is a cascade reaction.  These cascade reactions can be used by the cell to communicate within the cell, or between cells in the body.  They can cause genes within the DNA to create more proteins for different biological activity, or cause more enzymes to be produced, which assists many more chemicals to be formed. (9-23)

Cell transductance (communication through these sensors / receptors), can open the cell walls to a flood of calcium ions, or increase the flow of glucose, adrenaline, and insulin across the membrane.  These sensors can cause the synthesis of good cholesterol versus bad cholesterol, can cause chemicals to dilate blood vessels, and cause the creation of NO, nitric oxide, to support the cells to produce chemicals to quench free radicals.  Because medicinal mushrooms have their own life to live, which in many respects is very similar to an animal’s cell life they have all of the essential amino acids and minerals. 

Remember, fungi breathe oxygen and exhale carbon dioxide, just as humans do; the mushroom cell needs and uses the same basic building blocks.  Fungi therefore contain all the essential amino acids, nucleotides, transition metals, vitamins, including B12, C, niacin, D, L-ergothioneine and a large contingent of enzymes to make the process work.  The components of Mushroom blends, are the very same that our cells need. The scientist can create blends according to the health challenges for consumption.  These certain mushroom blends are not a neutraceutical mix of chemicals put together in a lab.  It is an ancient living life form, and has the correct ratio and amounts of two to four thousand biological chemicals.  Specific mushroom species have evolved along side animals, and man is consuming this whole food, reaping the benefit of chemistry that was explicitly designed for a complete healthful life.  (24-33)

Bibliography

1) Dastrun et al. (2004), Molecular events associated with reactive oxygen species and cell cycle progression in mammalian cells, Dept. cell biology, Institute of Biomembranes, Utrecht University, The Netherlands, Online Pub.

2) Kakkura B., (2006), Variations in erythrocyte antioxidant glutathione peroxidase activity during the menstrual cycle, Dept of Obstetrics and Gynecology, University of Siena, Italy, Online Pub

3) Jeffery Klein, (2003), Susan Ackerman, Oxidative stress, cell cycle, and neurodegeneration, J. Clin Invest, 111;785-793

4) Nagy Z, Esiri, M (1998), The cell division cycle and the pathophysiology of Alzheimer’s disease.  Neuroscience, 87; 731-739,

5) Lee P. (2004), Mechanism of neuronal death in Down’s syndrome. J. Neural Trausm, Supp 57; 233-245

6) Kanman K, Jain S. (2000), Oxidative stress and apoptosis. Pathophysiology; 7; 153-163

7) Dirk Grundemann et al, (2004), Discovery of the ergothioneine, Transporter Department of Pharmachology, University of Cologne, Germany
 

8) Kutner& Jablonska, (2000), Vitamin D deficiency associated with cancers, Grant 2002: Hansen & Hamberg, 2001: Online Pub

9) Billaudel B, Barakat, L. (1998) Vitamin D3 deficiency and alterations of glucose metabolism in rat endocrine pancreas, Diabetes Metabolism 24, 344-350

10) S.P. Wasser, Medicinal mushrooms as a source of antitumor and immunomodulating polysaccharides (2002), Applied Microbial Biotechnology 60, pp258-274

11) Borchers AT, Stern JS, Hackman RM (1999) Mushrooms, tumors and immunity, Soc. Exp Biol Med 221; pp 281-293

12) Fullerton SA, Samadi AA, (2000), Induction of apoptosis in human prostatic cancer cells with beta-glucan from Maitake, Mol Urol 4: pp7-13

13) Breene W., Nutritional and Medicinal Calue of Specialty Mushrooms (1989), J. of food protection vol 53: No. 10, pp 883-894

14) Nathon Sharon, Halina Lis (1993), Carbohydrates in Cell Recognition, , Scientific America, Jan 1993

15) So-Young Won and Eun-Hee Park (2005), Anti-inflammatory and related pharmacological activities of cultured mycelia and fruiting bodies of Cordyceps militaris, , College of Pharmacy, Sookmyung Women’s Unicersity, Seoul 140-742, South Korea, Journal of Ethnopharmacology, Vol 96, issue 3, 15 Jan 2005 p 555-561

16) Chiou et al, 2000, Protein constituent contributes to the hypotensive and vasorelaxant activities of Cordyceps sinensis, Life Sciences 66 (2000), pp 1369-1376

17) Ingber et al, 1990 D. Ingber, T. Fujita, Synthetic analogs of fumagillin that inhibit angiogenesis and suppress tumor growth, Nature 348 (1990), pp 555-557

18) Koh et al, 2003 J.H. Koh, K.M. Kim, Ant fatigue and anti stress effects of the hot water fraction from mycelia of Cordyceps sinesis, Biological and Pharmaceuetin 26 (2003), pp 691-694

19) Bok et al, 1999 J.W. Bok, L. Lermer, J. Chilton, H.G. Klingerman, Antitumor sterols from the mycelia of Cordyceps sinensis, Phytochemistry 51 (1999), pp 891-898.

20) Bourlon, P. M., Billaudel, B& Faure-Dussert, A. (1999), Influence of vitamin D3 deficiency and 1, 25 dihydroxyvitamin D3 on de novo insulin biosynthesis in the islets of the rat endocrine pancreas, Journal of Endocrinology, 160, 87-95

21) Ohno, R., Imai, K. Yokomaku, S. & Yamada, K. (1975) Antitumor effect of protein bound polysaccharide preparation, PSK against 3-methylcholanthrene induced fibrosarcoma in C57BL/6 mice. Gann 66 697-681

22) Matsunaga, K., Oguchi, Y, Ando T, (1980) Effect of PSK on intestinal immune system in tumor bearing mice.  Proceedings of the Japanese Cancer Association, 29th Annual meeting, p145

23) Muto, S. Kobayashi, A. (1982) Structure and antitumor effect of PSK (Kreston): mechanistic aspects of the antitumor activity. Proceedings of 2ndInternational Conference of Immunopharmachology, p 308

24) Muto, S., Kobayashi, A. (1983) Structural analysis and antitumor effect of PSK, Proceedings of 13th International Congress of Chemotherapy, Vienna: part 287, pp 37-40

25) Morimasa, K. Yamana, S. Matsueda, H. (1980) Immunostimulent therapy with protein bound polysaccharide preparation in patients with SLE or RA. Clinical Immunology 12: 393-398

26) Aoki T (1984) Fenichei RL, Chirgis MA, Immune modulating agents and their mechanisms, Immunol Stud 25, 62-77

27) Fujimiya Y, Yamamoto H, Noji M (2000) Peroral effect on tumor progression of soluable B-1,6 glucans prepared by acid treatment from Agaricus blazei, Agaricaceae Higher Basidiomycetes, Int. J Med Mushrooms 2: pp43-49

28) Che Ys, Lin Lz, Clinical observation of therapeutic effects of JinShuBao on coronary heart disease, hyperlipidemia, and blood rheology. Chinese traditional herbal drugs 1996;27 (9) pp 552-553

29) Kiho T, Yamane A, Polysaccharides in fungi. XXXVI. Hypoglycemic activity of a polysaccharide (CS-F30) from the cultured mycelia of Cordyceps sinensis and its effect on glucose metabolism in  mouse liver. Biol Pharm Bull (1996);; 19(2) p294-296

30) Shao G. You Zj, Treatment of hyperlipidemia with Cordyceps sinensis; a double blind placebo control trial. Int j oriental Med 1990;15(2);77-80

31) Mizuno T. et al Antitumor active polysaccharides isolated from the fruiting body of Hericium erinaceum, an edible and medicinal mushroom called yamabushitake Biosci, Biotech, Biochem 56 (2), 347-348 (1992)

32)S. Konno, H Tazaki et al, A possible hypoglycemic effect of Maitake mushroom on type 2 diabetic patients, Diabetic Medicine, Vol 18 Issue 12 p 1010 Issue 12 Dec 2001

33) Kaoru Nagai, Akiko Chiba et al, Dilinoleoyl-phosphatidylethanolamine from Hericium erinaceum protects against ER stress dependent Neuro2a cel

Species of Medicinal Mushrooms

Scientific Name(s): Cordyceps sinensis (Berk.) Sacc. Family: Clavicipitaceae
 
C. sinensis is a black, blade-shaped fungus found primarily in the high altitudes on the Tibetan plateau in China.
 
Cordyceps is a genus of ascomycete fungi that includes about 400 described species.  All Cordyceps species are endoparasitoids. The best known of the genus is Cordyceps sinensis which gives rise to the vegetable caterpillar, a precious ingredient in Chinese traditional medicines. 
 
Wild cordyceps is rare. This mushroom is parasitic and grows on and derives its nutrients from moth caterpillars. In the fall, the fungal mycelia infect the caterpillar. The fungal infestation kills the caterpillar by early summer of the following year, thus releasing the fruiting body.  The wild form of C. sinensis is harvested, while the principal fungal mycelium ( Paecilomyces hepiali Chen) is cultivated aseptically.
 
The fruiting body and attached mycelium of cordyceps has been used in Chinese culture for centuries. In traditional Chinese medicine, it is valued for its activity in restoring energy, promoting longevity, and improving quality of life.  C. sinensis affects numerous human body systems including the circulatory, respiratory, and immune systems, as well as the liver, kidneys, and sex organs. Cordyceps has been used as an adjuvant in cancer therapy.
 
Seven classes of natural chemical constituents are found in wild C. sinensis including proteins, peptides, all essential amino acids, and polyamines; saccharides and sugar derivatives; sterols; nucleosides (including adenine, uracil, uridine, guanosine, thymidine, and deoxyuridine); fatty acids and other organic acids; vitamins (including B 1 , B 2 , B 12 , E, and K); and inorganic elements.2, 5 Cordycepin and other adenosine derivatives,mannitol, several unique sterols and their glycosides, polysaccharides, and cyclic peptides have been identified.

Over 2000 patients with various medical disorders have been involved in clinical trials using Cs-4 in China.  Cs-4 is a strain of the wild cordyceps sinensis and has been studied extensively in China.  The chemical and pharmacological profiles are similar to natural cordyceps sinensis and most of the research available was completed using Cs-4.  In traditional Chinese medicine, cordyceps sinensis has been used to treat male impotence and other types of sexual dysfunction.  Numerous animal studies and clinical trials have studied the effects of cordyceps sinensis on sexual function.In both animal and human clinical studies, cordyceps sinensis has shown renal protective effects against nephrotoxicity of aminoglycosides and cyclosporin A.  Cordyceps sinensisalso has demonstrated hepatoprotective effects in an animal study 7 and in clinical trials.  A hypoglycemic effect has been documented in animal studies. 8, 9, 10.  Investigators also have reported enhanced immune system activity in animal and in vitro studies with cordyceps sinensis.  Cordyceps sinensis has been used as an adjunct in cancer treatment and appears to improve tolerance to the adverse effects associated with radiation and chemotherapy.  The anti-inflammatory properties of cordyceps also have been reviewed; however, the mechanism of action has been elucidated. 3 

Sexual dysfunction

Clinical data

In several placebo-controlled, double-blind studies, patients with reduced sexual drive are typically treated with Cs-4 (3 g/day) for approximately 2 months. In elderly patients, clinical improvement of sexual drive and function for the Cs-4 group was statistically significant as compared with the control group.  There was an increase in 24-hour urine 17-ketosteroids in the Cs-4-treated patients; thus Cs-4 may affect sexual drive through the sex hormone systems or through a direct action on the sexual center of the brain and sexual organs. 2, 11, 12

Hyperlipidemia

Clinical data

Cs-4 also has been used in the treatment of hyperlipidemia and may have a hypocholesterolemic effect. 2, 13  In a double-blind, placebo-controlled clinical trial involving 273 patients, the Cs-4 group had a reduction in triglycerides after only 1 month of treatment.  Overall, half of the patients on Cs-4 therapy (3 g/day) had reductions in total cholesterol and triglycerides, and a significant increase in high-density Lipoprotein. 2 

Aging

Clinical data

In a double-blind, placebo-controlled trial, elderly patients with senescence-related symptoms had significant improvements in tolerance to cold ( P < 0.001), fatigue ( P < 0.001), dizziness ( P  < 0.001), tinnitus ( P= 0.001), frequent nocturia ( P= 0.004), hyposexuality ( P = 0.05), and amnesia ( P = 0.003). Patients were randomly assigned and received either Cs-4 (3 g/day) or placebo for 3 months.  There was a concurrent increase in red blood cell superoxide dismutase (SOD) activity ( P < 0.001). Reduction in SOD is recognized as one of the factors related to aging and may lead to accumulation of excessive oxygen-free radicals and oxidative damage to cells. 2

Arrhythmias

Clinical data

In a 3-month, open-label clinical trial, Cs-4 was used to treat 38 elderly patients with various arrhythmias.  The investigators concluded that Cs-4 was effective in treating patients with tachyarrhythmia and bradyarrhythmia, and the longer the therapy duration, the better the clinical improvement. The majority of patients with supraventricular arrhythmias experienced partial to complete recovery in the electrocardiograms. 3, 14 

Heart failure

Clinical data

A 26-month trial using Cs-4 (3 to 4 g/day) in combination with standard therapy (digoxin, hydrochlorothiazide, isosorbide dinitrate, furosemide, lanatoside, dopamine, and dobutamine) was studied in 64 chronic heart failure patients.  Patients using Cs-4 as an adjuvant treatment reported improvement in general physical, emotional, and psychological well-being as compared with controls.  There were no statistically significant differences in mortality between the two groups.  Overall, patients taking Cs-4 had statistically significant improvements in the shortness of breath /fatigue index ( P < 0.01), general physical condition ( P  < 0.05), emotional-psychological condition ( P < 0.05), and sexual drive ( P < 0.001) as compared with controls. 2 

Chronic obstructive pulmonary disease

Clinical data

In an open-label, clinical trial, patients with chronic obstructive pulmonary disease reported improvements in cough, phlegm, appetite, vitality, and pulmonary symptoms after treatment with Cs-4 (3 g/day for 3 weeks) compared with controls.  There was a significant increase in SOD activity ( P < 0.001) compared with baseline. In another open-label, clinical trial, patients with chronic renal dysfunction also had significant increases in SOD activity ( P < 0.001) compared with pretreatment levels after treatment with Cs-4 (5 g/day for 4 weeks). 2

Respiratory

Clinical data

More than 5 clinical studies (all approximately 4 weeks in duration) demonstrated significant clinical improvements ( P< 0.01) in respiratory symptoms (including chronic bronchitis, bronchial asthma, and cor pulmonale) after administration of a cordyceps-containing medication. Dosages ranged from 3 to 4.5 g/day of Cs-4 for 2 to 12 weeks.  When Cs-4 was used in combination with oxygen and other drugs in treating patients with cor pulmonale (right-sided heart failure), improvements were seen in respiratory and heart function as well as in sleep and emotional-spiritual state.  The combined use of Cs-4 (3 g/day) with astemizole (10 mg/day) and ketotifen (2 mg/day) was effective in treatment of asthma as compared with the controls treated with Western medicine alone ( P< 0.05). A potential mechanism may involve Cs-4 reducing the production of IgE (which will reduce the asthma attack) through T H1 and T H2 immune responses. 3, 15

Renal function

Clinical data

C. sinensis may improve kidney function and have renal protective effects against nephrotoxic chemicals. Cs-4 (6 g/day for 30 days) was effective in improving renal function in 30 patients with chronic renal failure.  Compared with pretreatment levels (not necessarily a valid reference point), investigators reported significant improvement in serum creatinine ( P < 0.02), red blood cell count ( P < 0.05), anemia ( P< 0.02), creatinine clearance ( P < 0.001), and blood urea nitrogen ( P < 0.01). Another study found similar significant improvements as well as reduction in urinary protein ( P< 0.01).  Results from other studies suggest improvement of renal function by C. sinensis linked with involvement of T-cell-mediated immune functions. In one study, elderly patients (53 to 73 years of age) with no history of renal disease were treated IM or IV with amikacin (0.4 g/day for 6 days) with either placebo or C. sinensis (6 g/day for 7 days) for the treatment of an acute infection.  After the therapy, the accumulated 24-hour urinary N-acetyl-beta-D-glucosaminidase (NAG) level was increased by 4 times in controls compared with double in those patients receiving C. sinensis ( P< 0.05). NAG is an index for aminoglycoside-induced renal damage. 3, 16

Hepatitis

Clinical data

In a 3-month, open-label trial of 33 patients, a cultivated mycelial product of C. sinensis was effective in the treatment of chronic active hepatitis B. Investigators reported after the treatment that the thymol turbidity test (TTT) and serum glutamic-pyruvic transaminase (SGPT) either improved or returned to normal.  In addition, serum albumin increased and gamma globulin decreased significantly. No significant changes were seen in TTT or ALT in another study of 22 patients with hepatic cirrhosis; although significant improvements were seen in serum albumin ( P < 0.01) and gamma globulin ( P < 0.05). Other references referred to in this report have shown similar results. 3

Diabetes

Clinical data

In a randomized trial involving 42 patients with diabetes, Cs-4 (3 g/day for 30 days) was found to be an effective treatment in combination with traditional Chinese herbs compared with a control group given only the herbs.  Patients in the treatment group previously had a positive urinary protein test; after treatment, half of these patients tested negative compared with no change in the controls. 3

Leukemia and immunocompetent patients

Clinical data

One study demonstrated enhanced activity of natural killer (NK) cells in patients with leukemia and in immunocompetent individuals.  It also prevented reductions in NK cell activity in immunosuppressed mice. 3

Lung Cancer Clinical Data

In 59 patients with terminal lung cancer, administration of Cs-4 (2 to 3 g/day) resulted in more patients completing radiation and/or chemotherapy compared with a control group ( P < 0.01). Cs-4 also may minimize bone marrow impairment because patients in the Cs-4 treatment group had normal blood counts as compared with the control group ( P< 0.01). One study concluded that the fruiting body of C. sinensis contains growth inhibitors against tumor cells. 3 , 6

Animal Data

Investigators studied the effect of a fraction of mycelia of C. sinensis (150 mg/kg/day) for its antifatigue and antistress effects against a stimulus (swimming endurance capacity) in vivo using rats and mice.  The researchers concluded the fraction of mycelia of C. sinensis has antifatigue and antistress effects on the following stress indices: serum level measurements of total cholesterol, lactate dehydrogenase, alkaline phosphatase, aspartate transaminase, and alanine transaminase. 12, 17  Investigators have reported the following pharmacological activities of natural C. sinensis on the cardiovascular system in animal studies in vivo or with isolated organs: Dilation of arteries and improvement of nutritional blood supply to organs and extremities; reduction of heart rate; antiarrhythmic effects; effects against acute myocardial ischemia and stress-induced myocardial infarction; and effects of thrombosis and anti-aggregation of platelets.

Bibliography

1. Huang KC. The Pharmacology of Chinese Herbs . 2nd ed. Boca Raton, FL: CRC Press; 1999.
2. Zhu JS, Halpern GM, Jones K. The scientific rediscovery of an ancient Chinese herbal medicine: Cordyceps sinensis : part I. J Altern Complement Med . 1998;4:289-303.
3. Zhu JS, Halpern GM, Jones K. The scientific rediscovery of a precious ancient Chinese herbal regimen: Cordyceps sinensis : part II. J Altern Complement Med . 1998;4:429-457.
4. Stamets P. Novel antimicrobials from mushrooms. HerbalGram . 2002;54:28-33.
5. Huang LF, Liang YZ, Guo FQ, Zhou ZF, Cheng BM. Simultaneous separation and determination of active components in Cordyceps sinensis and Cordyceps militarris by LC/ESI-MS. J Pharm Biomed Anal . 2003;33:1155-1162.
6. Bok JW, Lermer L, Chilton J, Klingeman HG, Towers GH. Antitumor sterols from the mycelia of Cordyceps sinensis . Phytochemistry . 1999;51:891-898.
7. Liu YK, Shen W. Inhibitive effect of Cordyceps sinensis on experimental hepatic fibrosis and its possible mechanism. World J Gastroenterol . 2003;9:529-533.
8. Zhao CS, Yin WT, Wang JY, et al. CordyMax Cs-4 improves glucose metabolism and increases insulin sensitivity in normal rats. J Altern Complement Med . 2002;8:309-314.
9. Balon TW, Jasman AP, Zhu JS. A fermentation product of Cordyceps sinensis increases whole-body insulin sensitivity in rats. J Altern Complement Med . 2002;8:315-323.
10. Hockaday TD. Two herbal preparations, Cordyceps Cs4 and Cogent db: do they act on blood glucose, insulin sensitivity, and diabetes as “viscous dietary fibers?” J Altern Complement Med . 2002;8:403-405.
11. Hsu CC, Tsai SJ, Huang YL, Huang BM. Regulatory mechanism of Cordyceps sinensis mycelium on mouse Leydig cell steroidogenesis. FEBS Lett . 2003;543:140-143.
12. Hsu CC, Huang YL, Tsai SJ, Sheu CC, Huang BM. In vivo and in vitro stimulatory effects of Cordyceps sinensis on testosterone production in mouse Leydig cells. Life Sci . 2003;73:2127-2136.
13. Koh JH, Kim JM, Chang UJ, Suh HJ. Hypocholesterolemic effect of hot-water extract from mycelia of Cordyceps sinensis . Biol Pharm Bull . 2003;26:84-87.
14. Chiou WF, Chang PC, Chou CJ, Chen CF. Protein constituent contributes to the hypotensive and vasorelaxant activities of Cordyceps sinensis . Life Sci . 2000;66:1369-1376.
15. Kuo YC, Tsai WJ, Wang JY, Chang SC, Lin CY, Shiao MS. Regulation of bronchoalveolar lavage fluids cell function by the immunomodulatory agents from Cordyceps sinensis . Life Sci . 2001:68:1067-1082.
16. Shahed AR, Kim SI, Shoskes DA. Down-regulation of apoptotic and inflammatory genes by Cordyceps sinensis extract in rat kidney following ischemia/reperfusion. Transplant Proc . 2001;33:2986-2987.
17. Koh JH, Kim KM, Kim JM, Song JC, Suh HJ. Antifatigue and antistress effect of the hot-water fraction from mycelia of Cordyceps sinensis . Biol Pharm Bull . 2003;26:691-694

Photographs of the Cordycep: http://ocid.nacse.org/research/cordyceps/html/images.html

More information: http://en.wikipedia.org/wiki/Cordyceps