IM-3

$33.50
RV97

IM-3 is a unique combination of Cordyceps sinensis and Ganoderma lucidum for strengthening and supporting a healthy immune response. IM-3 promotes the activation of immune effector cells: lymphocytes, macrophages, and natural killer cells.

Ingredients
Cordyceps sinensis (contains purified polysaccharide)
Ganoderma lucidum (contains ganopoly 30% extract)

 

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-3

60 x 500mg Capsules

Product Overview

IM-3 is a unique combination of two exceptional mushroom compounds for strengthening and supporting a healthy immune response. IM-3 features Cordyceps sinensis, a profoundly researched medicinal mushroom. Ganoderma another kingly mushroom, is traditionally used to help stimulate the body's natural defences against tumour and other debilitating conditions.

Actions

Enhances immune function, surveillance and modulation

Activation of immune effector cells: lymphocytes, macrophages, and natural killer cells

Supports renal function

Antiviral

Antibacterial

Apoptotic

Cytotoxic

Indications 

Weakened cellular immunity

Recurrent infections

Viral infections

Upper respiratory tract infections

Bacterial infections

Chronic renal failure

Chemotherapy

Chronic fatigue

Suggested Use: 

1 capsule twice daily, with Chemo or Radio therapy 4-6 caps daily.

Warning: 

Not to be used with anti-inflammatories, e.g. Berberine, Emodin and SB-120.

Cordyceps sinensis

Cordyceps sinensis is a mushroom that has been used for over 2,000 years in China as a treatment for a variety of conditions including infectious diseases. The available evidence suggests any efficacy of C. sinensis, as an anti-infective therapeutic would be related to a role as an activator of innate immune responses. The ability of C. sinensis to activate pro-inflammatory responses in macrophages in vitro and induce protective responses against intracellular pathogens in vivo was investigated, and its mode of action was characterized. It was found that C. sinensis activates murine macrophages to produce a variety of pro-inflammatory cytokines. IFN-gamma synergizes with C. sinensis to amplify this response. C. sinensis is hence thought to activate macrophages by engaging Toll-like receptors and inducing mitogen-activated protein kinase (MAPK) pathways characteristic of inflammatory stimuli.

 

Immune function

Cordyceps sinensis purified polysaccharide (CSPS) was found to significantly enhance ovalbumin (OVA)-induced splenocyte proliferation in OVA-immunized mice at a suitable dose. OVA-specific IgG, IgG1 and IgG2b antibody levels in serum were significantly enhanced by these extracts and CSPS compared with the OVA control group.[1]

CSPS activates murine macrophages to produce a variety of pro-inflammatory cytokines. IFN-γ synergizes with CSPS to amplify this response. Available evidence supports the hypothesis that CSPS activates macrophages by engaging Toll-like receptors and inducing mitogen-activated protein kinase (MAPK) pathways characteristic of inflammatory stimuli.[2]

An acidic polysaccharide (APS) was isolated from the extract of Cordyceps and it decreased virus titers in the bronchoalveolar lavage fluid, and the lung of mice infected with influenza A virus and increased survival rate. Furthermore, APS increased TNF-α and IFN-γ levels in mice when compared with those of untreated mice. APS enhanced nitric oxide (NO) production and induced iNOS mRNA and protein expressions in RAW 264.7 murine macrophage cells. The induction of mRNA expression of cytokines including IL-1β, IL-6, IL-10, and TNF-α was also observed. These results demonstrated that APS might have beneficial therapeutic effects on influenza A virus infection at least in part by modulation of the immune function of macrophages.[3]

Cordyceps extract had an anti-influenza effect that was associated with stable body weight and reduced mortality. The anti-viral effect of Cordyceps extract on influenza infection was mediated presumably by increased IL-12 expression and greater number of NK cells.[4]

The effect of various extracts and a polysaccharide from the edible mycelia of Cordyceps sinensis on cellular and humoral immune response against ovalbumin in mice was investigated. The edible mycelia of Cordyceps sinensis (Berk.) Sacc. were sequentially extracted by petroleum ether, ethyl acetate, ethanol and ultrasonic water-bath (75 °C), and the water extract was further isolated by Sephadex G-100 to afford a petroleum ether extract (PE), ethyl acetate extract (EAE), ethanol extract (EE), glycoprotein (GP) and a purified polysaccharide (PS). In combination with component analysis, the isolated PS showed d-Glc, d-Man, l-Ara and d-Gal in a molar ratio of 8:90:1:1. The average molecular weight of PS was determined as 8.3 × 104. The immunomodulatory potentials of these samples (PE, EAE, EE, GP and PS) at three dose levels on the cellular and humoral immune responses of ICR mice against ovalbumin (OVA) were studied. Administration with these extracts was found to significantly enhance the Con A- and OVA-induced splenocyte proliferation in OVA-immunized mice at a suitable dose (p < 0.05 or p < 0.01). OVA-specific IgG, IgG1 and IgG2b antibody levels in serum were significantly enhanced by these extracts and PS compared with the OVA control group (p < 0.05, p < 0.01 or p < 0.001).[5]

 

Cordyceps and Renal function

The effect of Cordyceps Sinensis on renal function in patients with chronic renal failure (CRF) was detected before and after the therapy. Patients receiving Bailing capsules experienced significant (P<0.01) reduction in blood urea nitrogen (BUN) and serum creatinine (Scr), and an increase in ECT20 minER and creatinine clearance rate (Ccr). Patients receiving a placebo had no significant (P>0.05) increase in ECT20minER, Ccr, BUN and Scr. Between the two groups, the treatment group had significantly reduced (P<0.05) BUN and Scr levels, and increased (P<0.01) in ECT 20 minER and Ccr. It was hence suggested that Cordyceps Sinensis could improve the renal function and delay the progression of the patients.[6]

The effects of Cordyceps sinensis (CS) on the metabolism of body protein, and intra- and extra-cellular amino acids in patients with chronic renal failure (CRF), and on the rates of protein synthesis in rats with CRF were studied. After patients with CRF were treated by CS, the Leu, Ile, Thr, Lys, Cys, and Tyr concentrations in plasma approached the normal levels. In one sample of skeletal muscle the Thr and Lys concentrations approached the normal, whereas both the intracellular and extra-cellular Val concentrations were still remarkably decreased as compared with the normal controls. Moreover, the nitrogen flow rate (Q), rates of protein synthesis (S) and catabolism (C), and amino nitrogen utilization ratio (S/Q) in patients with CRF and the SL% /d and SM% /d in rats with CRF were significantly increased as compared with those before CS treatment. CS can hence notably improve the amino acid metabolism, promote the body’s protein synthesis in patients with CRF, and increase the rates of SL% /d and SM% /d in rats with CRF.[7]

Synchronous measurements of renal function and T-cell subsets were taken in 51 cases of chronic renal failure (CRF) patients. An obvious decrease of OKT3, OKT4, OKT4/OKT8 was found in CRF (P<0.01), with OKT4 and OKT4/OKT8 being proportional to plasma albumin and Hb levels (P<0.05). After administration of Cordyceps sinensis, improvement of renal function and OKT4, OKT4/OKT8 were confirmed. This indicates that cellular immune function was decreased in CRF, and administration of Cordyceps sinensis may improve renal function and enhance the cellular immune function in those suffering CRF.[8]

Animal model of chronic renal failure (CRF) was induced in wistar rats by 5/6 nephrectomy. It was found that Cordyceps sinensis (CS) had a mitogenic effect on spleen lymphocytes, and is capable of increasing the production of IL-2 from splenocytes of the CRF rats. IL-2 absorbency of the splenocytes was promoted by CS. CS also exhibited such therapeutic effects in CRF animals as to decrease the levels of BUN and serum creatinine, and to increase the levels of haemoglobin. These results indicate that CS may have a regulative effect on cellular immunity in CRF rats.[9]

In order to evaluate the effect of Cordyceps sinensis (CS) on aminoglycoside (AG) induced nephrotoxicity, gentamycin was imposed on the young and old rats with CS administration. The renal tubular injury was ameliorated as evidenced by less prominent increment of BUN, SCr, sodium excretion, urinary NAGase and less severity of histopathological changes as compared with the control. In addition, the use of CS could promote an earlier recovery of renal oxygen consumption insulin clearance, and sodium absorption in isolated perfused kidney from CS treated intoxicated rat than that from control. Possible mechanisms of CS on drug-induced nephrotoxicity include: (1) Accelerating the regeneration of tubular cells; (2) Protecting the sodium pump activity of tubular cells; (3) Attenuating the tubular cell lysosome hyperfunction stimulated by phagocytosis of AG as well as decreasing the tubular cell lipoperoxidation in response to toxic injury; (4) Reducing the tissue Ca2+ content.[10]

A water-soluble polysaccharide (CPS-2), isolated from cultured Cordyceps sinensis, was obtained and characterized by hot-water extraction, anion-exchange and gel permeation chromatography. CPS-2 was found to be mostly of alpha- (1-->4)-D-glucose and alpha- (1-->3)-D-mannose, branched with alpha- (1-->4,6)-D-glucose every twelve residues on average. CPS-2 had a molecular weight of 4.39x10(4) Da. The protective effect of CPS-2 on the model of chronic renal failure was established by fulgerizing kidney. The changes in blood urea nitrogen and serum creatinine revealed that CPS-2 could significantly relieve renal failure caused by fulgerizing kidney.[11]

 

Ganoderma lucidum

Cellular Immunity

Cellular immunity is a sensitized small lymphocyte-mediated immune response produced by the differentiation and proliferation of T lymphocytes. There are at least two kinds of effector cells for cellular immunity, namely, T helper (Th) cells and T killer (Tc) cells, which is also called cytotoxic T cells (CTL). Th cells may also indirectly kill target cells by releasing cytokines. The influence of G. lucidum on cellular immune function is an important aspect of its immunomodulatory effects.[12] A series of investigations demonstrated that the cell-mediated immune function was also enhanced by G. lucidum. The mRNA expression and production of IFN-γ were significantly increased in the T lymphocytes.[13]

 

Effect of Ganoderma on Mononuclear Phagocyte System

Macrophages can polarize into M1 phenotype (classically activated macrophages) or M2 phenotype (alternatively activated macrophages) in response to different microenvironmental signals, which are involved in many different pathogeneses. In general, M1 is responsible for pathogen clearance, inflammation, and tumour-suppressing response, while the M2 performs immunosuppressive and tumour-promoting functions. It has been recognized that improvement on M1 polarization, instead of M2 polarization, may be health beneficial.[14]

Sun et al. revealed that G. lucidum polysaccharide peptide (Gl-PS) might have the potential to promote macrophage M1 polarization induced by LPS. The level of M1 stimulating factor IL-6, IL-12, and TNF-α stimulated by LPS was upregulated in a dose- dependent manner after treatment of Gl-PS. In contrast, the level of M2 stimulating factor arginase I and IL-10 was reduced by Gl-PS, demonstrating the potential of Gl-PS to promote M1 polarization versus M2.[15]

 

Effect of Ganoderma on the Natural Killer Cells

Natural killer (NK) cells are considered to be part of the innate defence system. NK cells, in contrast to cytotoxic T cells, have the ability to kill certain tumour cells in vitro without prior sensitization. In addition, NK cells display Fc-receptors for IgG and are important mediators of antibody-dependent cell-mediated cytotoxicity. In some cases, NK cells have spontaneous cytotoxic activity on target cells, participating in the occurrence of hypersensitivity reactions and autoimmune diseases.

A number of reports indicated that water extracts isolated from G. lucidum fruiting bodies or G. lucidum polysaccharides could enhance activity of NK cells in in vivo experiments. Chien et al. (2004) reported that a fucose-containing glycoprotein fraction (F3) (10–100 μg/mL), isolated from the water-soluble extracts of G. lucidum, was applied to human umbilical cord blood mononuclear cells (MNCs) in vitro. After 7 days of culture, cell phenotypic analysis by flow cytometry showed that CD14+CD26+ monocytes/macrophages, CD83+CD1a+ dendritic cells, and CD16+CD56+ NK cells increased by 2.9%, 2.3%, and 1.5%, respectively, indicating that F3 quantitatively influenced NK cell activities. They also found that F3 is not harmful to human cells in vitro; and after F3 treatment, NK cell-mediated cytotoxicity was significantly enhanced by 31.7% at effector/target cell ratio (E/T) 20:1, but was not altered at E/T 5:1.[16] [17]

 

Fig. The immunomodulatory effects of Ganoderma on various immune cells[18]

 

Maturation and Function of Dendritic Cells

Dendritic cells (DCs) are the most powerful professional antigen-presenting cells (APCs) in the body. DCs are the initiator of immune response and play a unique role in the induction of immune response. Mature DCs can activate the initial T cells effectively.

Cao and Lin, firstly established the culture of murine bone marrow-derived DC in vitro and further explored whether G. lucidum polysaccharides (Gl-PS) have regulatory effects on maturation and function of DC. Gl-PS was shown to promote not only the maturation of cultured murine bone marrow derived DC in vitro, but also the immune response initiation induced by DC.[19]

Zhu et al. compared polysaccharides extracted from three different types of herbs, including Astragalus membranaceus, Ganoderma lucidum and Radix ophiopogonis, all of which showed immunostimulatory effects on DC maturation. Polysaccharides from Ganoderma lucidum has the strongest potency in phenotypic and functional aspects for DC while the extracts from Radix ophiopogonis is the weakest. Interestingly, NO may provide a feedback stimulation for DC maturation and DC maturation was partially dependent upon endocytosis of polysaccharides, both of which have not been reported previously. Therefore, the increase of NO level as well as the increase in polysaccharide endocytosis could be the novel strategies for improved innate response and immunotherapy through DC maturation.[20]

 

Epstein-Barr virus

In this study, five triterpenoids were identified as the major phytochemicals in G. lucidum. Pharmacological evaluation in vitro demonstrated that these triterpenoids were able to inhibit the activation of Epstein-Barr virus (EBV) antigens at 16 and 3.2 nmol to different extents. The triterpenoids also inhibited the activity of telomerase, which is an enzyme associated with EBV infection. Molecular docking has further confirmed the inhibitory effect of compound 1 on telomerase. The physicochemical properties of the triterpenoids elucidated in the present study provide a primary outline of their drug-like properties.[21]

Ganoderma polysaccharide (GP) treatment has been found to significantly increase the expression of both TNF-alpha and IFN-gamma in splenocytes in a dose-dependent manner, and significantly increase cytotoxic T lymphocyte cytotoxicity and NK activity.[22] The changes in IL-1 were correlated with those for IL-6, IFN-γ, CD3, CD8, and NK activity, and IL-2 changes correlated with those for IL-6, CD8, and NK activity. The results suggest that subgroups of cancer patients may be responsive to GP in combination with chemotherapy/radiotherapy.[23]

 

Effects of Ganoderma lucidum polysaccharides on immune cells[24]

Immune cells

Effects

Macrophages

Enhance phagocytosis

Promote IL-1, TNFα production and TNFα mRNA expression

Prevent oxidant tBOOH-induced oxidative injury

Protect mitochondrial membrane and alleviate membrane injury by free radicals

Increase [Ca2+]i

Induce IP3 and DAG formation

Increase PKC activity

Activate macrophages via TLR4 and TLR4-modulated protein kinase signalling pathways

Neutrophils

Increase in PKC, MAPK, HCK and tyrosine kinase Lyn activities

Inhibit spontaneous and Fas-induced apoptosis by activation of Akt-regulated signalling pathways

Dendritic cells

Promote maturation and immune response initiation induced by DC

Promote cytotoxicity of specific CTL induced by DC

Increase IFNγ and granzyme B production and mRNA expression

Induce activation and maturation of human DC by the NF-κB and p38 MAPK pathways

Natural killer cells

Enhance activity of NK cells

Increase NK-cell-mediated cytotoxicity

T lymphocytes

Increase lymphocyte proliferation induced by ConA and MLC

Promote IL-2, IFN-γ production

Increase DNA synthesis and enhance activity of DNA polymerase α

Increase the percentage of CD5+, CD4+ and CD8+ T-lymphocytes

Increased production of IP3 and DAG

Increase activities of PKA and PKC

B lymphocytes

Increase lymphocyte proliferation induced by LPS

Increase in secretion of immunoglobulin

Stimulate expression of PKC

Reduced mucosal specific IgA response of young adult mice orally immunized with cholera toxin

 

Cancer

Antitumor activity and underlying mechanisms of ganopoly, the refined polysaccharides extracted from Ganoderma lucidum, were investigated in mice. Treatment of mice bearing sarsoma-180 with oral Ganoderma polysaccharide (GP) significantly increased the expression of both TNF-alpha and IFN-gamma (at both mRNA and protein levels) in splenocytes in a dose-dependent manner. Moreover, treatment with GP could also significantly increase cytotoxic T lymphocyte cytotoxicity and NK activity in mice. This indicates that GP has anti-tumour activity with a broad spectrum of immuno-modulating activities and may represent a novel promising immunotherapeutic agent in cancer and chronic diseases hepatopathy treatment.[25]

Ganopoly is an aqueous polysaccharide fraction extracted from G. lucidum by patented biochemical technique and has been marketed as an over-the-counter product for chronic diseases including cancer and hepatopathy in many Asian countries. The anti-tumour effect and the underlying mechanisms of Ganopoly was explored in mice and human tumour cell lines. In addition, Ganopoly enhanced concanavalin A-stimulated proliferation of murine splenocytes by 35.3% at 10 mg/mL, and stimulated the production of nitric oxide in thioglycollate-primed murine peritoneal macrophages in a concentration-dependent manner over 0.05-10 mg/mL. Addition of Ganopoly at 1 mg/mL to murine peritoneal macrophages also potentiated lipopolysaccharide-induced nitric oxide production by 64.2%. Treatment of healthy mice or mice bearing sarcoma-180 with oral Ganopoly over 20-100 mg/kg for 7 day significantly increased the expression of both TNF-alpha and IFN-gamma (at both mRNA and protein levels) in splenocytes in a dose-dependent manner. Moreover, treatment of Ganopoly over 20-100 mg/kg significantly increased cytotoxic T lymphocyte cytotoxicity and NK activity in mice. The overall findings indicate that Ganopoly had antitumor activity with a broad spectrum of immuno-modulating activities and may represent a novel promising immunotherapeutic agent in cancer treatment.[26]

The effects of water-soluble Ganoderma lucidum polysaccharides on the immune functions of patients with advanced lung cancer was investigated. The changes in IL-1 were correlated with those for IL-6, IFN-gamma, CD3, CD8, and NK activity (P < .05), and IL-2 changes were correlated with those for IL-6, CD8, and NK activity. The results suggest that subgroups of cancer patients might be responsive to Ganopoly in combination with chemotherapy/radiotherapy. Further studies are needed to explore the efficacy and safety of Ganopoly used alone or in combination with chemotherapy/radiotherapy.[27]

 

Mushroom-derived active compounds - Ganoderma and Cordyceps

Han Chunchao  and Jian-You Guo (2011) hypothesized that the mushroom-derived active compound may be a potential strategy for increasing survival in response to influenza virus infection through the stimulation of host innate immune response. The validity of the hypothesis can be tested by immune response to influenza infection as seen through survival percentage, virus clearance, weight loss, natural killer cell cytotoxicity, Tumour Necrosis Factor-α (TNF-α) and Interferon-gamma (IFN-γ) levels, lytic efficiency in the spleens of mice and inducible nitric oxide synthase mRNA expressions in RAW 264.7 murine macrophage cells. The hypothesis may improve people's quality of life, reduce the medical cost of our healthcare system and eliminate people's fears of influenza outbreak.[28]

In contrast to bacterial infectious diseases, viral diseases cannot be treated by common antibiotics and specific drugs are urgently needed. Antiviral effects are described not only for whole extracts of mushrooms but also for isolated compounds. They could be caused directly by inhibition of viral enzymes, synthesis of viral nucleic acids or adsorption and uptake of viruses into mammalian cells. These direct antiviral effects are exhibited especially by smaller molecules. Indirect antiviral effects are the result of the immuno-stimulating activity of polysaccharides or other complex molecules.[29]

Se, Zn, and Mg present in mushrooms may play a direct or indirect role in their anti-influenza virus nature. They may provide prophylactic protection against influenza infection via stimulation of host innate immune response.[30]

 

Antifatigue functions

Ganoderma lucidum, Cordyceps sinensis, Lentinus edodes, Tremella fuciformis, and Hericium erinaceus could all effectively increase swimming endurance and reduce BUN and lactic acid level, with Ganoderma lucidum and Cordyceps sinensis showing most significant stimulating effect on Lactate dehydrogenase activity. Cordyceps sinensis has been found to have vasodilation effect on blood vessels. It helps to avoid fatigue by redistribution and increase blood flow to supply enough oxygen and nutrients to essential organs and muscles. Feng and co-workers found that the aqueous phosphate buffer saline extracts of C. sinensis can stimulate nitric oxide production and endothelium-derived hyperpolarizing factor (EDHF) to reduce arterial pressure and induce the endothelium-dependent vasodilation effect.[31] The active component of adenosine in G. lucidum has also been found as an important contributor to vasodilation, which can reduce blood viscosity, inhibit platelet aggregation, and improve blood oxygen supply capacity.

Cordyceps sinensis extracts can increase the energy content in liver cell because they induce the relaxation of liver blood vessels, leading to increase in liver blood flow. In this case, the liver can work effectively to promote blood circulation and clean blood to carry more oxygen and nutrient for energy metabolism in mitochondria. Ganoderma lucidum can increase glycogen storage, improve BUN clearance rate, limit lactic acid accumulation, and significantly improve LDH activity. It can also inhibit lipid peroxidation and scavenge nitric oxide and superoxide anion.[32]

Ganoderma lucidum, was applied in this preliminary study on fatigue and quality of life of CFS. In comparison to placebo, a significant increase in quality of life (p=0.005) with a decrease in VAS scores (p=0.010) of those who received Ganoderma lucidum extracts was observed 4 weeks after the first dose. An increase in serum cortisol was observed in volunteers who took Ganoderma lucidum extract for 12 weeks, but not placebo. Satisfaction of volunteers with 12-week Ganoderma lucidum extract was significantly higher than those with the placebo group (p<0.001) while side effects, diarrhea and nausea, from both groups were not significantly different (p = 0.785). It is concluded that Ganoderma lucidum extract could be potentially effective in the treatment of fatigue and improve quality of life in CFS patients.[33] [34]

 

Renal function

Studies have showed effects of Ganoderma lucidum and its extracts on renal injury. The hot water extract of Ganoderma lucidum dose-dependently reduced mouse kidney lipid peroxidation induced by 95% ethanol.[35] Other studies indicated that Ganoderma extract significantly reduced oxidative damage and apoptosis in human proximal tubular epithelial cells induced by human serum albumin[36], while Lingzhiols, extracted from Ganoderma lucidum, could inhibit TGF-β/Smads signaling pathways.[37] Moreover, a novel proteoglycan from Ganoderma lucidum fruiting bodies conferred significant amelioration on renal function and morphologic injuries in diabetic nephropathy mice.[38]These studies suggest that Ganoderma lucidum and its extracts have wide renal protective activities and a good application prospect in different kidney diseases.

Zhong et al. verifies, for the first time, that Ganoderma lucidum polysaccharide peptide has beneficial effects on cerebral ischemia reperfusion (IR) caused acute kidney injury (AK). The protective effect of GLPP against renal ischemia reperfusion injury may be attributed to the inhibition of NADPH oxidase-dependent production of ROS and the increase of free radical-scavenging capacity for the balance of the oxidation/antioxidant system, improving mitochondrial dysfunction and ER stress-dependent apoptosis, which subsequently alleviates AKI caused by IR. Our study suggests that GLPP may be developed as a candidate drug for preventing AKI.[39]

 

Fig. Summary of anti-renal diseases effects of bioactive components of G. lucidum[40]

  

References

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[2] Jordan JL, Sullivan AM, Lee TD. Immune activation by a sterile aqueous extract of Cordyceps sinensis: mechanism of action. Immunopharmacol Immunotoxicol. 2008; 30(1):53-70. doi: 10.1080/08923970701812332 .

[3] Ohta Y et val. In Vivo Anti-influenza Virus Activity of an Immunomodulatory Acidic Polysaccharide Isolated from Cordyceps militaris Grown on Germinated Soybeans. J. Agric. Food Chem. 2007, 55, 25, 10194-10199. https://doi.org/10.1021/jf0721287

[4] Anti-influenza Effect of Cordyceps Militaris Through Immunomodulation in a DBA/2 Mouse Model. J Microbiol, 52 (8), 696-701 Aug 2014, DOI: 10.1007/s12275-014-4300-0

[5] Yalin Wu, Hongxiang Sun, Feng Qin, Yuanjiang Pan, Cuirong Sun. Phytotherapy Research. Effect of various extracts and a polysaccharide from the edible mycelia of Cordyceps sinensis on cellular and humoral immune response against ovalbumin in mice. 2006 Volume 20 Issue 8, Pages 646-652

[6] Chai Wenhua, Ya N Shunzhang, Liu Hui. Zhong Guo Dang Dai Yi Yao. 2009; The effect of Cordyceps Sinensis on renal function of patients with CRF 16(17): 28-29.

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[11] Wang Y, Yin H, Lv X, Wang Y, Gao H, Wang M. Fitoterapia. 2010 Protection of chronic renal failure by a polysaccharide from Cordyceps sinensis.Jul;81(5):397-402. Epub 2009 Dec 4.

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[13] Zhang QH, Lin ZB (1999) Effect of Ganoderma lucidum polysaccharides B on TNFα and INFγ production and their mRNA expression. J Beijing Med Univ 31:179–183

[14] Wang N, Liang H, Zen K (2014) Molecular mechanisms that influence the macrophage m1-m2 polarization balance. Front Immunol 5:614

[15] Sun LX, Lin ZB, Lu J, Li WD, Niu YD, Sun Y, Hu CY, Zhang GQ, Duan XS (2017) The improvement of M1 polarization in macrophages by glycopeptide derived from Ganoderma lucidum. Immunol Res 65(3):658–661

[16] Chien CM, Cheng JL, Chang WT, Tien MH, Tsao CM, Chang YH et al (2004) Polysaccharides of Ganoderma lucidum alter cell immunophenotypic expression and enhance CD56+ NK-cell cytotoxicity in cord blood. Bioorg Med Chem 12:5603–5609

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[18] Lin, Z., & Yang, B. (Eds.). (2019). Ganoderma and Health. Advances in Experimental Medicine and Biology. doi:10.1007/978-981-32-9421-9

[19] Cao LZ, Lin ZB (2002) Regulation on maturation and function of dendritic cells by Ganoderma lucidum polysaccharides. Immunol Lett 83(3):163–169

[20] Zhu N, Lv X, Wang Y, et al. Comparison of immunoregulatory effects of polysaccharides from three natural herbs and cellular uptake in dendritic cells. Int J Biol Macromol. 2016;93(Pt A):940-951. doi:10.1016/j.ijbiomac.2016.09.064

[21] Zheng DS, Chen LS. Triterpenoids from Ganoderma lucidum inhibit the activation of EBV antigens as telomerase inhibitors. Exp Ther Med. 2017;14(4):3273‐3278. doi:10.3892/etm.2017.4883

[22] Gao Y, Gao H, Chan E, Tang W, Xu A, Yang H, Huang M, Lan J, Li X, Duan W, Xu C & Zhou S. Antitumour activity and underlying mechanisms of ganopoly, the refined polysaccharides extracted from Ganoderma lucidum, in mice. Immunol-Invest. 2005; 34(2): 171-98

[23] Jordan JL, Sullivan AM, Lee TD. Immune activation by a sterile aqueous extract of Cordyceps sinensis: mechanism of action. Immunopharmacol Immunotoxicol. 2008; 30(1):53-70. doi: 10.1080/08923970701812332 .

[24] Lin ZB. Cellular and molecular mechanisms of immuno-modulation by Ganoderma lucidum. J Pharmacol Sci. 2005;99(2):144‐153. doi:10.1254/jphs.crj05008x

[25] Gao Y, Gao H, Chan E, Tang W, Xu A, Yang H, Huang M, Lan J, Li X, Duan W, Xu C & Zhou S. Antitumour activity and underlying mechanisms of ganopoly, the refined polysaccharides extracted from Ganoderma lucidum, in mice. Immunol-Invest. 2005; 34(2): 171-98

[26] Yihuai Gao, Wenbo Tang, Xihu Dai, He Gao, Guoliang Chen, Jinxian Ye, Eli Chan, Hwee Ling Koh, Xiaotian Li, Shufeng Zhou. Journal of Medicinal Food. Summer 2005, 8(2): 159-168. doi:10.1089/jmf.2005.8.159.

[27] Yalin Wu, Hongxiang Sun, Feng Qin, Yuanjiang Pan, Cuirong Sun. Effects of Water-Soluble Ganoderma lucidum Polysaccharides on the Immune Functions of Patients with Advanced Lung Cancer. 2005 Journal of Medicinal Food

[28] Chunchao H, Guo JY. A Hypothesis: Supplementation With Mushroom-Derived Active Compound Modulates Immunity and Increases Survival in Response to Influenza Virus (H1N1) Infection. Evid Based Complement Alternat Med, 2011, DOI: 10.1093/ecam/neq037

[29] Brandt CR, Piraino F. Mushroom antivirals. Recent Res Dev Antimicrob Agents Chemother. 2000;4:11–26.

[30] Wang L, Hou Y. Determination of Trace Elements in Anti-Influenza Virus Mushrooms. Biol Trace Elem Res, 143 (3), 1799-807 Dec 2011 DOI: 10.1007/s12011-011-8986-0

[31] M. G. Feng, Q. G. Zhou, and G. H. Feng, “Vasodilating effect of cultured Cordyceps sinensis (Berk) Sacc. mycelia in anesthetized dogs,” Zhong Yao Tong Bao, vol. 12, no. 12, pp. 41–60, 1987.

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[33] Soksawatmakhin S, Boonyahotra W. Preliminary study of the applications of Ganoderma lucidum in chronic fatigue syndrome. Journal Of Asian Association of Schools Of Pharmacy - Volume 2, 2013. Pages: 262-268

[34] Geng P, Siu KC, Wang Z, Wu JY. Antifatigue Functions and Mechanisms of Edible and Medicinal Mushrooms. Biomed Res Int. 2017;2017:9648496. doi:10.1155/2017/9648496

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