IM-1
IM-1 contains medicinal mushroom compounds to balance humoral and cellular immunity and increase white blood cell count. IM-1 is an immunomodulator capable of stimulating diverse immunological functions.
| Ingredients |
|---|
| Trametes versicolor |
| Polyporus umbellatus |
| Phellinus robiniae |
| Lentinula edodes |
| Ganoderma lucidum |
| Astragalus membranaceus |
Other Ingredients: Vegetable cellulose (hypromellose); Vegetable Stearic Acid; Microcrystalline Cellulose and Vegetable Magnesium Stearate.
Does Not Contain: Wheat, gluten, soy, milk, eggs, fish, crustacean shellfish, tree nuts, peanuts
IM-1 - Medicinal Mushrooms formula
60 x 500mg Capsules
Actions
Modulates immune response
Enhance immune function
Stimulates white blood cell production
Hepatoprotective
Indications
Immune Deficiency
Hyperglycaemia
Deficiency fatigue
Neurasthenia
Hepatocirrhosis
Bronchial cough
Suggested Use:
1 to 2 capsules daily
With Chemo or Radiotherapy 8 to 12 capsules daily
Caution:
None noted
Warning:
Not to be used with anti-inflammatories, e.g. Berberine, Emodin and SB-120.
The number of mushrooms on Earth is estimated at 140,000, yet maybe only 10% (approximately 14,000 named species) are known. 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 polysaccharides with anti-tumor and immunostimulating properties. Many Basidiomycetes mushrooms contain biologically active polysaccharides in fruit bodies, cultured mycelium, and culture broth.
Mushroom Formula One is a combination of some of the best-studied and most effective immunomodulators available. The mushrooms, studied below are extracts with proven abilities to regulate inflammation, shrink tumors and reduce the side effects of radiotherapy and chemotherapy.
Ageing-Related Shifts in Immune Functions
Altered membrane fluidity
Increased apoptosis perhaps due to decline in CD28 expression and IL-2 production
CD20 overexpression on lymphocytes
Increased CAMs expression on lymphocytes
Old cells may have greater levels of messenger RNA for 3 mitotic inhibitors
Decrease number of HLA class I and II antigenic sites on lymphocytes
Increase in activated T-cell expressing DR molecules
Decreased proportion of T, B, and NK cells expressing CD62L and increased density per cell of this adhesion receptor expression
Upregulation of L-selectin per T-cell
Shift in lymphocyte population to contain more CD3-NK cells and CD3+CD56+ T-cells
CD3 downregulation and CD50 upregulation on T-cells affecting activation and proliferation
Increased T-cell death by fas/fas-ligand mediated response in presence of IL-2
Heightened density of CD5 on B-cells
Decreased number of monocytes with LFA-1
Decreased ability of dendritic cells to stimulate T-cell secretion of IFN -γ and IL2
Anti-cancer
Aqueous extracts from fruit bodies and mycelia of various higher Basidiomycetes were studied in search for reliable biological effects. In vitro and in vivo experiments were conducted. The results showed that the aqueous extracts demonstrated various types of marked biological actions: an increased production of reactive oxygen forms by neutrophil cells of human peripheral blood; a significant mitogenic activity in a wide range of concentrations; stimulation on production of inflammatory cytokines interleukin 1-É and interleukine-8 by peripheral blood cells; a decrease in both average tumor size in mice with transplanted melanoma B16 and a manifestation of tumorous intoxication; and a prolongation in the survival rate of such mice (Shamtsyan et al., 2004).
Inflammation, Immune and Diabetes
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 (Poucheret et al., 2006).
Maitake D-fraction
Maitake possesses a significant ability to stimulate white blood cells known as macrophages. These specialized white blood cells phagocytize or engulf foreign particles including cancer cells, bacteria, and cellular debris. This fraction consists of polysaccharide compounds (beta-1,6 glucan and beta-1,3 glucan) and protein.
While other medicinal mushrooms have shown to have similar beta-glucan constituents, it was discovered that the beta-glucans found in the maitake D-fraction have a unique and complex structure. The biggest difference was a greater number of branching side chains. It was thought that the greater the degree of branching, the higher the likelihood the beta-glucan fraction will reach and activate a greater number of immune cells. The maitake MD-fraction actually bind to receptors on the outer membranes of macrophages and other white blood cells including natural killer (NK) cells and cytotoxic T-cells (Tc).
According to preliminary data, maitake betaglucan fractions appear to help reduce the side effects of conventional chemotherapy (and radiation) while at the same time enhancing its effectiveness. In 1994, a pilot study was carried out on 63 cancer patients reporting a total effective rate against solid tumors at higher than 95% and the effective rate against leukemia higher than 90%. In a preliminary study, 165 patients with advanced cancer were given maitake extract. In patients being treated with chemotherapy, 90% of the patients experienced a reduction in the side effects common to chemotherapy including hair loss, decreased white blood cell counts, nausea, vomiting, and loss of appetite. Maitake was shown to effectively reduce pain levels in 83% of the patients. The results were best in breast, lung, and liver cancers. A significant improvement was also reported in symptoms or regression of tumors in 73.3% of patients with breast cancer, 66.6% in lung cancer, and 46.6% in liver cancer (Nanba, 1995).
Ganoderma
Several major substances with potent immunomodulating action have been isolated from Ganoderma. These include polysaccharides (in particular d-glucan), proteins (e.g., Ling Zhi-8) and triterpenoids. The major immunomodulating effects of these active substances derived from Ganoderma 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 (TNF), and interferons. There is evidence indicating that d-glucans from medicinal mushrooms induce biological response by binding to membrane complement receptor type three (CR3, M2 integrin, or CD11b/CD18) on immune effector cells. The ligand-receptor complex is then internalized, intriguing a series of molecular events such as the activation of the nuclear factor NF-B.
Immunosuppressive effects by Ganoderma components have also been observed. The therapeutic effects of Ganoderma, such as anti-cancer and anti-inflammatory effects, have been associated with its immunomodulating effects. However, further studies are needed to determine the molecular mechanisms of the immunomodulating effects of Ganoderma mushrooms (Yihuai Gao et al., 2004). It has been shown that an extract of Ganoderma lucidum (Reishi or Ling-Zhi) polysaccharides (EORP) exerts immunomodulating activities by stimulating the expression of inflammatory cytokines from mouse spleen cells (Hsu et al., 2004).
Hericium has been found to enhance the cytolytic activity of total splenocytes towards Yac-1 cells in a dose-dependent manner. It indirectly activates the cytolytic ability of NK cells via the induction of IL-12 in total splenocytes, and possibly via other immuno-mediators or cellular components (Yim et al., 2007).
Hericium erinaceus fruit body
The extraction and activity of polysaccharides from Hericium erinaceus has been investigated. Polysaccharides from Hericium erinaceus extracted via water decoction have been found to possess remarkable immune-enhancing activity (Han et al., 2008).
Reishi mushroom fruit body
Ganoderma Lucidum Polysaccharide has been found to counteract the inhibition of mice splenocyte proliferation and IL-1 a and IL-2 mRNA expression induced by Prostaglandin E2.
After co-culture with PGE2 for 48 hours, the splenocyte proliferation was inhibited to some extent, and the difference was significant when the concentration of PGE2 was over 101mmol/L (P<0.01 compared with that before treatment with PGE2). The results co-culture with PGE2 at 20p~mol/L and GLP at different concentrations of 50, 100 and 200 mg/L showed that GLP at 100 mg/L or above had partial counteraction on PGE2-induced inhibition of splenocyte proliferation. After co-culture with PGE2 at 20mmol/L and GLP at 100 mg/L or above for 8 and 12 hours, the IL-la mRNA expression and IL-2 mRNA expression were inhibited in mice (P<0.05 or P<0.01 compared with that before treatment with GLP). GLP can counteract the inhibition of mice splenocyte proliferation and IL-la and IL-2 mRNA expression induced by PGE2 (Zhang et al., 2008).
Hepatoprotective Effects of Ganoderma lucidum Peptides on Immunological Liver Injury in Mice
The hepatoprotective effects of Ganoderma lucidum peptides (GLP) were researched on Bacille-Calmette-Gu’erin and lipopolysaccharide (BCG/LPS)-induced immunological liver injury in mice. The index of fiver and spleen in mice and ALT/AST activities in serum from the group at high dose were significantly lower than that of the model group (p<0.01). GLP at the doses significantly inhibited NO/MDA lever in liver and reduces of SOD/GSH-Px activity and GSH content in fiver (p<0.05-0.01). The five histopathological characteristics gradually straighten up. At the dose of 180 mg/kg bw GLP, the hepatoprotective effect is the best and the index is close to normal group’s. GLP hence possesses potent hepatoprotective effects against BCG/LPS-induced fiver damage in mice (Shi et al., 2008).
Experimental Study of Impact on Immunological Function in Tumor Bearing Mice Treated with Combination of GLP and DCN
The impacts of the combined therapy of ganoderma lucidum polysaccharide (GLP) and decorin (DCN) gene on immunological function and its anti-tumor effect in mice bearing S180 have been investigated. It was found in each treatment group that the growth of tumor was, on average, slowed down in volume, the proliferative rate of lymphocytes increased significantly (P<0.05), VEGF expression downgraded apparently, and the percentage of CD4+ CD25+ regulatory T cells in CD4+ T cells was reduced significantly. The combination of GLP and DCN gene can hence significantly improve the activity of immune system of tumor bearing mice and suppress tumor growth (Yang et al., 2009).
Astragalus / huang qi
There is a significant amount of experimental research on Astragalus capsule enhancing immunity. In an in vivo study, mice were administered Astragalus capsule at a dose of 200, 400 and 800mg/kg BW, respectively, once a day for 30-35 days. 7 indexes of immune function were then measured to judge the effect of Astragalus capsule on the immune system. All the examination results of the experimental group in comparison with the control group showed that transformation and proliferation of splenic lymphocyte were enhanced; and the quantity of the mice anti-body-producing cell and the sheep erythrocyte antibody levels in serum were also raised. The mononuclear macrophage ability to eliminate carbon and mononuclear celiac macrophage phagocytic activity increased; the delayed hypersensitivity accelerated; but the activity of NK cell was not raised significantly. It was hence suggested that Astragalus capsule could enhance immune function (Li et al., 2008).
Effect of Astragalus Polysaccharide on Immunological Function in Mice
The effect of astragalus polysaccharide (APS) on immunological function in mice has been investigated by the lymphocyte transformation test and delayed type hypersensitivity (DTH). Compared with the normal control group, APS could promote DTH, PFC, HC50 and phagocytosis of peritoneal macrophages, but had no effect on lymphocyte proliferation. APS could hence stimulate the immunological function in mice via different mechanisms (Wang et al., 2009).
An Experimental Study on the Protective Effect of on Immunological Liver Injury in Mice
The protective effect of milkvetch root injection, red peony root injection and their combination to mouse liver injury induced by bacillus calmettc-guerin vaccine (BCG) and Lipopolysaccharide (LPS) were investigated. Milkvetch root injection, red peony root injection, and their combination significantly decreased the levels of serum ALT, AST, LDH and MDA, but enhanced SOD activity in the liver, and the curative results (indicated as levels of ALT, AST, LDH, SOD, MDA) of combination injection significantly excelled those of both milkvetch root injection (P<0.05, P<0.05, P<0.05, P<0.01, P>0.05) alone or red peony root injection (P<0.01, P<0.01, P<0.05, P<0.01, P<0.05) alone. Milkvetch root injection and red peony root injection can protect liver from acute injury induced by BCG + LPS in mice. The combined use of milkvetch root injection and red peony root injection can produce significantly better protective effect than their single use (Chen et al., 2008).
Study on activation of mouse peritoneal macrophage by Astragalus Saponin
The immunomodulatory effect of Astragalus Saponin (AS) was investigated on macrophages, and the mechanisms of its immunomodulation was explored. AS was found to significantly increase NO synthesis, and enhance the capacity of mice peritoneal macrophages for cytotoxicity to carcinoma cells. AS can enhance the immune functions of macrophages, and the increase in intracellular Ca2+ may be one of the mechanisms of its immunomodulatory effects (Yang et al., 2008).
Hericium erinaceus
Soluble components of Hericium erinaceus induce NK cell activation via production of interleukin-12 in mice splenocytes
The effect of water extracts of Hericium erinaceus (WEHE) on natural killer (NK) cell-based anticancer activities was investigated. WEHE enhanced the cytolytic activity of total splenocytes towards Yac-1 cells in a dose-dependent manner; however, this activation was not observed when the NK cells isolated from the splenocytes were treated with WEHE. Furthermore, the treatment with antibodies against IL-12 abolished the effect of WEHE on splenocyte-derived cytolytic activity. RT-PCR and ELISA analyses showed the induction of IL-12 and IFN-gamma in the WEHE-treated splenocytes. WEHE indirectly activates the cytolytic ability of NK cells via the induction of IL-12 in total splenocytes, and possibly via other immuno-mediators or cellular components (Yim et al., 2007; Nagai et al., 2006).
Macrophage activation and structural characteristics of purified polysaccharides from the liquid culture broth of Hericium erinaceus
Recently, a number of bioactive molecules, including antitumor agents, have been identified in various higher basidiomycetes mushrooms. Polysaccharides are the best known and most potent mushroom derived substances that display immuno-pharmacological properties. The water-soluble crude polysaccharide HEB-P, which was obtained from the liquid culture broth of Hericium erinaceus by ethanol precipitation, was fractionated by DEAE cellulose and Sepharose CL-6B column chromatography. This fractionation process resulted in two polysaccharide fractions that were termed HEB-NP Fr I and HEB-AP Fr I. Of the fractions, HEB-AP Fr I was able to upregulate the functional events mediated by activated macrophages, such as production of nitric oxide (NO) and expression of cytokines (IL-1β and TNF-α). Results indicate that HEB-AP Fr I was a low molecular mass polysaccharide with a laminarin-like triple helix conformation of the β-1,3-branched-β-1,2-mannan (Lee et al., 2009).
Hericium erinaceus enhances doxorubicin-induced apoptosis in human hepatocellular carcinoma cells
It has been demonstrated that the Hericium erinaceus (HE) mushroom, which primarily consists of polysaccharides, possesses anti-tumor activities. However, the mechanisms by which HE inhibits human hepatocellular carcinoma growth remain unknown. HE has been found to act as an enhancer to sensitize doxorubicin (Dox)-mediated apoptotic signaling, and this sensitization can be achieved by reducing c-FLIP expression via JNK activation and enhancing intracellular Dox accumulation via the inhibition of NF-κB activity. These findings suggest that HE in combination with Dox serves as an effective tool for treating drug-resistant human hepatocellular carcinoma (Lee & Hong, 2010).
Hypoglycemic effects
Rats administered with Hericium had significantly lower elevation rates of blood glucose level than those not administered with Hericium. The effects on blood glucose, serum triglyceride and total cholesterol levels were more significant in the rats fed daily with Hericium at doses of 100 mg kg-1 body weight (bw), compared to 20 mg kg-1 bw (p < 0.05) (Wang et al., 2004).
Coriolus versicolor
Coriolus versicolor polysaccharide peptide slows progression of advanced non-small cell lung cancer
Non-small cell lung cancer (NSCLC) is a leading cause of cancer deaths, and over 60% of patients present with advanced stages. Although polysaccharide peptides (PSP), isolated from the fungus Coriolus versicolor, have been reported to have anti-tumor effects, its clinical efficacy has not been properly evaluated. In a clinical study, thirty-four patients, with no significant difference in their baseline demographic, clinical or tumor characteristics, or previous treatment regimes (P>0.05), were recruited into each of the PSP and control arms. After a 28-day treatment, there was a significant improvement in blood leukocyte and neutrophil counts, serum IgG and IgM, and percent of body fat among the PSP, but not the control, patients (P<0.05). Although the evaluable PSP patients did not improve in NSCLC-related symptoms, there were significantly less PSP patients withdrawn due to disease progression, than their control counterparts (5.9 and 23.5%, respectively; P=0.04; OR 4.00). There was no reported adverse reaction attributable to the trial medications. PSP treatment hence appears to be associated with slower deterioration in patients with advanced NSCLC (Tsang et al., 2003).
References
CHEN Yingli, XING Jie, LV Yueshan, YU Yang. Gui Yang Yi Xue Yuan Xue Bao. 2008; An Experimental Study on the Protective Effect of on Immunological Liver Injury in Mice 33(4): 357-359.
HAN Wei, LIU Rui-li, ZHANG Xiao-jian. An Hui Yi Yao. 2008; Extraction and activity of polysaccharide from Hericium erinaceus 12(9): 793-794.
Hsien-Yeh Hsu, Kuo-Feng Hua, Chun-Cheng Lin, Chun-Hung Lin, Jason Hsu and Chi-Huey Wong. Extract of Reishi Polysaccharides Induces Cytokine Expression via TLR4-Modulated Protein Kinase Signaling Pathways. The Journal of Immunology, 2004, 173: 5989-5999
Kaoru Nagai, Akiko Chiba, Toru Nishino, Takeo Kubota, Hirokazu Kawagishi. Dilinoleoyl-phosphatidylethanolamine from Hericium erinaceum protects against ER stress-dependent Neuro2a cell death via protein kinase C pathway. The Journal of Nutritional Biochemistry Volume 17, Issue 8, August 2006, Pages 525-530
Lee JS, Cho JY, Hong EK. 2009; Study on macrophage activation and structural characteristics of purified polysaccharides from the liquid culture broth of Hericium erinaceus. Carbohydrate Polymers. 78(1): 162-168
Lee JS, Hong EK. 2010; Hericium erinaceus enhances doxorubicin-induced
apoptosis in human hepatocellular carcinoma cells. Cancer Letters. 297(2):144-154
LI Feng-wen, QIN Hui-yan, ZHAO Peng, Li Bin, Zhang Jiehong, Huang Chaopei Liang Huili, Yang Jufeng, Yao Siyu. Wang Yanwu. Fu Weizhong, He Li, Liang Jian, Peng Liang. Yin Yong Yu Fang Yi Xue. 2008; Experimental research on Astragalus capsule enhancing immunity 14(6): 330-333
Myung-hyun YIM, Jang-woo SHIN, Jin-young SON, Se-mi OH, Seung-hyun HAN, Jung-hyo CHO, Chong-kwan CHO, Hwa-seung YOO, Yeon-weol LEE,
Chang-gue SON. Soluble components of Hericiumerinaceum induce NK cell activation via production of interleukin-12 in mice splenocytes. Acta PharmacologicaSinica Volume 28 Issue 6 Page 901 - June 2007
Nanba H. Results of non-controlled clinical study for various cancer patients using maitake D-fraction. Explore 1995;6:19-21.
Poucheret Patrick, Fons Françoise & Rapior Sylvie. Biological and Pharmacological Activity of Higher Fungi: 20-Year Retrospective Analysis. Cryptogamie, Mycologie, 2006, 27 (4): 311-333
Shamtsyan Mark, Konusova Valentina, Maksimova Yulia, Goloshchev Alexander, Panchenko Andrey, Simbirtsev Andrey, Petrishchev Nikolay, Denisova Nina. Immunomodulating and anti-tumor action of extracts of several mushrooms. Journal of Biotechnology Volume 113, Issues 1-3, 30 September 2004, Pages 77-83
SHI Yan-ling, HE Hui, ZHANG Sheng, HU Hao-yu, LIANG Run-sheng. Shi Pin Ke Xue. 2008; Hepatoprotective Effects of Ganoderma lucidum Peptides on Immunological Liver Injury in Mice 29(6): 415-418.
Tsang KW, Lam CL, Yan C, et al. 2003; Coriolus versicolor polysaccharide peptide slows progression of advanced non-small cell lung cancer Respiratory Medicine. 97(6):618-624
Wang Jinn Chyi, Hu Shu Hui, Wang JihTerng, Chen Ker Shaw and Chen Chia Yi. Hypoglycemic effect of extract of Hericium erinaceus, Journal of the Science of Food and Agriculture. 2004, Volume 85, Issue 4 , Pages 641 - 646
WANG Ting-xin, WANG Ting-xiang, WU Guang-chen, LIU Zheng-hao, XIA Li-ya. Shi Zhen Guo Yi Guo Yao. 2009; Effect of Astragalus Polysaccharide on Immunological Function in Mice 20(7): 1763-1764.
YANG Wan-fang, WANG Gui-qin, HAO Fang. Shi Jie Zhong Xi Yi Jie He Za Zhi. 2009; Experimental Study of Impact on Immunological Function in Tumor Bearing Mice Treated with Combination of GLP and DCN (4): 245-247.
YANG Xiao-Min, XU Xiao-Wu, LU He-Lian, ZHANG Tian-Yi. Zhong Guo Mian Yi Xue Za Zhi. 2008; Study on activation of mouse peritoneal macrophage by Astragalus Saponin 24(9): 804-809.
Yihuai Gao, Eli Chan & Shufeng Zhou. Immunomodulating Activities of Ganoderma, a Mushroom with Medicinal Properties. Food Reviews International, Volume 20, Issue 2 June 2004, pages 123 - 161
ZHANG Qun, LEI Linsheng, YU Chuanlin, WU Shuguang. Guang Zhou Zhong Yi Yao Da XueXue Bao. 2008; Counteraction of Ganoderma Lucidum Polysaccharide on the Inhibition of Mice Splenocyte Proliferation and IL-1 a and IL-2 mRNA Expression Induced by Prostaglandin E2 25(6): 549-552.
| Ingredients |
|---|
| Trametes versicolor |
| Polyporus umbellatus |
| Phellinus robiniae |
| Lentinula edodes |
| Ganoderma lucidum |
| Astragalus membranaceus |
Other Ingredients: Vegetable cellulose (hypromellose); Vegetable Stearic Acid; Microcrystalline Cellulose and Vegetable Magnesium Stearate.
Does Not Contain: Wheat, gluten, soy, milk, eggs, fish, crustacean shellfish, tree nuts, peanuts
IM-1 - Medicinal Mushrooms formula
60 x 500mg Capsules
Actions
Modulates immune response
Enhance immune function
Stimulates white blood cell production
Hepatoprotective
Indications
Immune Deficiency
Hyperglycaemia
Deficiency fatigue
Neurasthenia
Hepatocirrhosis
Bronchial cough
Suggested Use:
1 to 2 capsules daily
With Chemo or Radiotherapy 8 to 12 capsules daily
Caution:
None noted
Warning:
Not to be used with anti-inflammatories, e.g. Berberine, Emodin and SB-120.
The number of mushrooms on Earth is estimated at 140,000, yet maybe only 10% (approximately 14,000 named species) are known. 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 polysaccharides with anti-tumor and immunostimulating properties. Many Basidiomycetes mushrooms contain biologically active polysaccharides in fruit bodies, cultured mycelium, and culture broth.
Mushroom Formula One is a combination of some of the best-studied and most effective immunomodulators available. The mushrooms, studied below are extracts with proven abilities to regulate inflammation, shrink tumors and reduce the side effects of radiotherapy and chemotherapy.
Ageing-Related Shifts in Immune Functions
Altered membrane fluidity
Increased apoptosis perhaps due to decline in CD28 expression and IL-2 production
CD20 overexpression on lymphocytes
Increased CAMs expression on lymphocytes
Old cells may have greater levels of messenger RNA for 3 mitotic inhibitors
Decrease number of HLA class I and II antigenic sites on lymphocytes
Increase in activated T-cell expressing DR molecules
Decreased proportion of T, B, and NK cells expressing CD62L and increased density per cell of this adhesion receptor expression
Upregulation of L-selectin per T-cell
Shift in lymphocyte population to contain more CD3-NK cells and CD3+CD56+ T-cells
CD3 downregulation and CD50 upregulation on T-cells affecting activation and proliferation
Increased T-cell death by fas/fas-ligand mediated response in presence of IL-2
Heightened density of CD5 on B-cells
Decreased number of monocytes with LFA-1
Decreased ability of dendritic cells to stimulate T-cell secretion of IFN -γ and IL2
Anti-cancer
Aqueous extracts from fruit bodies and mycelia of various higher Basidiomycetes were studied in search for reliable biological effects. In vitro and in vivo experiments were conducted. The results showed that the aqueous extracts demonstrated various types of marked biological actions: an increased production of reactive oxygen forms by neutrophil cells of human peripheral blood; a significant mitogenic activity in a wide range of concentrations; stimulation on production of inflammatory cytokines interleukin 1-É and interleukine-8 by peripheral blood cells; a decrease in both average tumor size in mice with transplanted melanoma B16 and a manifestation of tumorous intoxication; and a prolongation in the survival rate of such mice (Shamtsyan et al., 2004).
Inflammation, Immune and Diabetes
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 (Poucheret et al., 2006).
Maitake D-fraction
Maitake possesses a significant ability to stimulate white blood cells known as macrophages. These specialized white blood cells phagocytize or engulf foreign particles including cancer cells, bacteria, and cellular debris. This fraction consists of polysaccharide compounds (beta-1,6 glucan and beta-1,3 glucan) and protein.
While other medicinal mushrooms have shown to have similar beta-glucan constituents, it was discovered that the beta-glucans found in the maitake D-fraction have a unique and complex structure. The biggest difference was a greater number of branching side chains. It was thought that the greater the degree of branching, the higher the likelihood the beta-glucan fraction will reach and activate a greater number of immune cells. The maitake MD-fraction actually bind to receptors on the outer membranes of macrophages and other white blood cells including natural killer (NK) cells and cytotoxic T-cells (Tc).
According to preliminary data, maitake betaglucan fractions appear to help reduce the side effects of conventional chemotherapy (and radiation) while at the same time enhancing its effectiveness. In 1994, a pilot study was carried out on 63 cancer patients reporting a total effective rate against solid tumors at higher than 95% and the effective rate against leukemia higher than 90%. In a preliminary study, 165 patients with advanced cancer were given maitake extract. In patients being treated with chemotherapy, 90% of the patients experienced a reduction in the side effects common to chemotherapy including hair loss, decreased white blood cell counts, nausea, vomiting, and loss of appetite. Maitake was shown to effectively reduce pain levels in 83% of the patients. The results were best in breast, lung, and liver cancers. A significant improvement was also reported in symptoms or regression of tumors in 73.3% of patients with breast cancer, 66.6% in lung cancer, and 46.6% in liver cancer (Nanba, 1995).
Ganoderma
Several major substances with potent immunomodulating action have been isolated from Ganoderma. These include polysaccharides (in particular d-glucan), proteins (e.g., Ling Zhi-8) and triterpenoids. The major immunomodulating effects of these active substances derived from Ganoderma 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 (TNF), and interferons. There is evidence indicating that d-glucans from medicinal mushrooms induce biological response by binding to membrane complement receptor type three (CR3, M2 integrin, or CD11b/CD18) on immune effector cells. The ligand-receptor complex is then internalized, intriguing a series of molecular events such as the activation of the nuclear factor NF-B.
Immunosuppressive effects by Ganoderma components have also been observed. The therapeutic effects of Ganoderma, such as anti-cancer and anti-inflammatory effects, have been associated with its immunomodulating effects. However, further studies are needed to determine the molecular mechanisms of the immunomodulating effects of Ganoderma mushrooms (Yihuai Gao et al., 2004). It has been shown that an extract of Ganoderma lucidum (Reishi or Ling-Zhi) polysaccharides (EORP) exerts immunomodulating activities by stimulating the expression of inflammatory cytokines from mouse spleen cells (Hsu et al., 2004).
Hericium has been found to enhance the cytolytic activity of total splenocytes towards Yac-1 cells in a dose-dependent manner. It indirectly activates the cytolytic ability of NK cells via the induction of IL-12 in total splenocytes, and possibly via other immuno-mediators or cellular components (Yim et al., 2007).
Hericium erinaceus fruit body
The extraction and activity of polysaccharides from Hericium erinaceus has been investigated. Polysaccharides from Hericium erinaceus extracted via water decoction have been found to possess remarkable immune-enhancing activity (Han et al., 2008).
Reishi mushroom fruit body
Ganoderma Lucidum Polysaccharide has been found to counteract the inhibition of mice splenocyte proliferation and IL-1 a and IL-2 mRNA expression induced by Prostaglandin E2.
After co-culture with PGE2 for 48 hours, the splenocyte proliferation was inhibited to some extent, and the difference was significant when the concentration of PGE2 was over 101mmol/L (P<0.01 compared with that before treatment with PGE2). The results co-culture with PGE2 at 20p~mol/L and GLP at different concentrations of 50, 100 and 200 mg/L showed that GLP at 100 mg/L or above had partial counteraction on PGE2-induced inhibition of splenocyte proliferation. After co-culture with PGE2 at 20mmol/L and GLP at 100 mg/L or above for 8 and 12 hours, the IL-la mRNA expression and IL-2 mRNA expression were inhibited in mice (P<0.05 or P<0.01 compared with that before treatment with GLP). GLP can counteract the inhibition of mice splenocyte proliferation and IL-la and IL-2 mRNA expression induced by PGE2 (Zhang et al., 2008).
Hepatoprotective Effects of Ganoderma lucidum Peptides on Immunological Liver Injury in Mice
The hepatoprotective effects of Ganoderma lucidum peptides (GLP) were researched on Bacille-Calmette-Gu’erin and lipopolysaccharide (BCG/LPS)-induced immunological liver injury in mice. The index of fiver and spleen in mice and ALT/AST activities in serum from the group at high dose were significantly lower than that of the model group (p<0.01). GLP at the doses significantly inhibited NO/MDA lever in liver and reduces of SOD/GSH-Px activity and GSH content in fiver (p<0.05-0.01). The five histopathological characteristics gradually straighten up. At the dose of 180 mg/kg bw GLP, the hepatoprotective effect is the best and the index is close to normal group’s. GLP hence possesses potent hepatoprotective effects against BCG/LPS-induced fiver damage in mice (Shi et al., 2008).
Experimental Study of Impact on Immunological Function in Tumor Bearing Mice Treated with Combination of GLP and DCN
The impacts of the combined therapy of ganoderma lucidum polysaccharide (GLP) and decorin (DCN) gene on immunological function and its anti-tumor effect in mice bearing S180 have been investigated. It was found in each treatment group that the growth of tumor was, on average, slowed down in volume, the proliferative rate of lymphocytes increased significantly (P<0.05), VEGF expression downgraded apparently, and the percentage of CD4+ CD25+ regulatory T cells in CD4+ T cells was reduced significantly. The combination of GLP and DCN gene can hence significantly improve the activity of immune system of tumor bearing mice and suppress tumor growth (Yang et al., 2009).
Astragalus / huang qi
There is a significant amount of experimental research on Astragalus capsule enhancing immunity. In an in vivo study, mice were administered Astragalus capsule at a dose of 200, 400 and 800mg/kg BW, respectively, once a day for 30-35 days. 7 indexes of immune function were then measured to judge the effect of Astragalus capsule on the immune system. All the examination results of the experimental group in comparison with the control group showed that transformation and proliferation of splenic lymphocyte were enhanced; and the quantity of the mice anti-body-producing cell and the sheep erythrocyte antibody levels in serum were also raised. The mononuclear macrophage ability to eliminate carbon and mononuclear celiac macrophage phagocytic activity increased; the delayed hypersensitivity accelerated; but the activity of NK cell was not raised significantly. It was hence suggested that Astragalus capsule could enhance immune function (Li et al., 2008).
Effect of Astragalus Polysaccharide on Immunological Function in Mice
The effect of astragalus polysaccharide (APS) on immunological function in mice has been investigated by the lymphocyte transformation test and delayed type hypersensitivity (DTH). Compared with the normal control group, APS could promote DTH, PFC, HC50 and phagocytosis of peritoneal macrophages, but had no effect on lymphocyte proliferation. APS could hence stimulate the immunological function in mice via different mechanisms (Wang et al., 2009).
An Experimental Study on the Protective Effect of on Immunological Liver Injury in Mice
The protective effect of milkvetch root injection, red peony root injection and their combination to mouse liver injury induced by bacillus calmettc-guerin vaccine (BCG) and Lipopolysaccharide (LPS) were investigated. Milkvetch root injection, red peony root injection, and their combination significantly decreased the levels of serum ALT, AST, LDH and MDA, but enhanced SOD activity in the liver, and the curative results (indicated as levels of ALT, AST, LDH, SOD, MDA) of combination injection significantly excelled those of both milkvetch root injection (P<0.05, P<0.05, P<0.05, P<0.01, P>0.05) alone or red peony root injection (P<0.01, P<0.01, P<0.05, P<0.01, P<0.05) alone. Milkvetch root injection and red peony root injection can protect liver from acute injury induced by BCG + LPS in mice. The combined use of milkvetch root injection and red peony root injection can produce significantly better protective effect than their single use (Chen et al., 2008).
Study on activation of mouse peritoneal macrophage by Astragalus Saponin
The immunomodulatory effect of Astragalus Saponin (AS) was investigated on macrophages, and the mechanisms of its immunomodulation was explored. AS was found to significantly increase NO synthesis, and enhance the capacity of mice peritoneal macrophages for cytotoxicity to carcinoma cells. AS can enhance the immune functions of macrophages, and the increase in intracellular Ca2+ may be one of the mechanisms of its immunomodulatory effects (Yang et al., 2008).
Hericium erinaceus
Soluble components of Hericium erinaceus induce NK cell activation via production of interleukin-12 in mice splenocytes
The effect of water extracts of Hericium erinaceus (WEHE) on natural killer (NK) cell-based anticancer activities was investigated. WEHE enhanced the cytolytic activity of total splenocytes towards Yac-1 cells in a dose-dependent manner; however, this activation was not observed when the NK cells isolated from the splenocytes were treated with WEHE. Furthermore, the treatment with antibodies against IL-12 abolished the effect of WEHE on splenocyte-derived cytolytic activity. RT-PCR and ELISA analyses showed the induction of IL-12 and IFN-gamma in the WEHE-treated splenocytes. WEHE indirectly activates the cytolytic ability of NK cells via the induction of IL-12 in total splenocytes, and possibly via other immuno-mediators or cellular components (Yim et al., 2007; Nagai et al., 2006).
Macrophage activation and structural characteristics of purified polysaccharides from the liquid culture broth of Hericium erinaceus
Recently, a number of bioactive molecules, including antitumor agents, have been identified in various higher basidiomycetes mushrooms. Polysaccharides are the best known and most potent mushroom derived substances that display immuno-pharmacological properties. The water-soluble crude polysaccharide HEB-P, which was obtained from the liquid culture broth of Hericium erinaceus by ethanol precipitation, was fractionated by DEAE cellulose and Sepharose CL-6B column chromatography. This fractionation process resulted in two polysaccharide fractions that were termed HEB-NP Fr I and HEB-AP Fr I. Of the fractions, HEB-AP Fr I was able to upregulate the functional events mediated by activated macrophages, such as production of nitric oxide (NO) and expression of cytokines (IL-1β and TNF-α). Results indicate that HEB-AP Fr I was a low molecular mass polysaccharide with a laminarin-like triple helix conformation of the β-1,3-branched-β-1,2-mannan (Lee et al., 2009).
Hericium erinaceus enhances doxorubicin-induced apoptosis in human hepatocellular carcinoma cells
It has been demonstrated that the Hericium erinaceus (HE) mushroom, which primarily consists of polysaccharides, possesses anti-tumor activities. However, the mechanisms by which HE inhibits human hepatocellular carcinoma growth remain unknown. HE has been found to act as an enhancer to sensitize doxorubicin (Dox)-mediated apoptotic signaling, and this sensitization can be achieved by reducing c-FLIP expression via JNK activation and enhancing intracellular Dox accumulation via the inhibition of NF-κB activity. These findings suggest that HE in combination with Dox serves as an effective tool for treating drug-resistant human hepatocellular carcinoma (Lee & Hong, 2010).
Hypoglycemic effects
Rats administered with Hericium had significantly lower elevation rates of blood glucose level than those not administered with Hericium. The effects on blood glucose, serum triglyceride and total cholesterol levels were more significant in the rats fed daily with Hericium at doses of 100 mg kg-1 body weight (bw), compared to 20 mg kg-1 bw (p < 0.05) (Wang et al., 2004).
Coriolus versicolor
Coriolus versicolor polysaccharide peptide slows progression of advanced non-small cell lung cancer
Non-small cell lung cancer (NSCLC) is a leading cause of cancer deaths, and over 60% of patients present with advanced stages. Although polysaccharide peptides (PSP), isolated from the fungus Coriolus versicolor, have been reported to have anti-tumor effects, its clinical efficacy has not been properly evaluated. In a clinical study, thirty-four patients, with no significant difference in their baseline demographic, clinical or tumor characteristics, or previous treatment regimes (P>0.05), were recruited into each of the PSP and control arms. After a 28-day treatment, there was a significant improvement in blood leukocyte and neutrophil counts, serum IgG and IgM, and percent of body fat among the PSP, but not the control, patients (P<0.05). Although the evaluable PSP patients did not improve in NSCLC-related symptoms, there were significantly less PSP patients withdrawn due to disease progression, than their control counterparts (5.9 and 23.5%, respectively; P=0.04; OR 4.00). There was no reported adverse reaction attributable to the trial medications. PSP treatment hence appears to be associated with slower deterioration in patients with advanced NSCLC (Tsang et al., 2003).
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