Article

Nutritional Food Active Hexose Correlated Compound (AHCC) Enhances Resistance against Bird Flu

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Abstract

AHCC is a nutritional food that has been broadly adopted in Japan as well as other countries. Several laboratories have demonstrated that AHCC has immune modulating effect. Increasing immunity against bird flu virus, H5N1, may help to prevent the next pandemic. We hypothesize that uptaking AHCC improve immunity against infection with this virus. Administration of AHCC for 7 days effectively improved survival rate by 30%, and this effect can last for 3 to 4 weeks. Our results indicate a potential role of AHCC in helping to build up immunity for preventing the pandemic of bird flu.

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... Active hexose correlated compound (AHCC) is a dietary supplement prepared from Basidiomycetes mushrooms, largely comprised of α-1,4-glucans [3]. Animal studies have demonstrated that AHCC increases survival during acute infections such as influenza virus [4][5][6], avian flu [5], West Nile virus [7], and opportunistic infections [8][9][10][11]. Our laboratory has shown that AHCC supplementation, even in small doses, increases survival of young mice against influenza infection [4,6]. ...
... Active hexose correlated compound (AHCC) is a dietary supplement prepared from Basidiomycetes mushrooms, largely comprised of α-1,4-glucans [3]. Animal studies have demonstrated that AHCC increases survival during acute infections such as influenza virus [4][5][6], avian flu [5], West Nile virus [7], and opportunistic infections [8][9][10][11]. Our laboratory has shown that AHCC supplementation, even in small doses, increases survival of young mice against influenza infection [4,6]. ...
... Many animal studies support the idea that AHCC enhances survival from several primary infections [4][5][6][7][8][9][10][11], a protective effect attributed to AHCC's actions on DCs, CD8 T cells and NK cells. The bioactive compound of AHCC is acetylated α-glucans but the exact mechanism of action is not known. ...
... Of the oligosaccharides in AHCC®, about 20% are α-1,4-glucans, of which a proportion is partially acylated, with a mean molecular weight around 5000 Daltons [6,7]. The effects of AHCC® on immune cells of humans and animals were reported in in vitro and in vivo studies, suggesting the possible help of its supplementation in defending the host against infections and malignancies via modulating the immune system [6,[9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28]. This review focuses on the reported effects of AHCC® on natural killer (NK) and T cells given their roles in host defense and inflammation [29][30][31][32][33][34], providing a platform for the better understanding of immune-mediated mechanisms and clinical implications of AHCC® and possibly other medical mushrooms in health and disease. ...
... The effect of AHCC® can be beyond H1NI influenza. The survival benefit by AHCC® supplementation was observed in mice infected with avian (bird) influenza virus H5N1 which could infect humans and poultry although its mechanism is yet to be demonstrated [15]. In fact, the mortality rate of H5N1 avian influenza is much higher than that of past influenza pandemics, reaching up to 60% [42]. ...
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Mushrooms have been used for various health conditions for many years by traditional medicines practiced in different regions of the world although the exact effects of mushroom extracts on the immune system are not fully understood. AHCC® is a standardized extract of cultured shiitake or Lentinula edodes mycelia (ECLM) which contains a mixture of nutrients including oligosaccharides, amino acids, and minerals obtained through liquid culture. AHCC® is reported to modulate the numbers and functions of immune cells including natural killer (NK) and T cells which play important roles in host defense, suggesting the possible implication of its supplementation in defending the host against infections and malignancies via modulating the immune system. Here, we review in vivo and in vitro effects of AHCC® on NK and T cells of humans and animals in health and disease, providing a platform for the better understanding of immune-mediated mechanisms and clinical implications of AHCC®.
... These glucans are thought to provide a carbohydrate that stimulates immune responses [8,9]. It has been previously reported that AHCC influences both natural immunity and acquisition immunity and is also effective against viral infection, Eumycota and other bacteria [10][11][12]. It has been reported that AHCC attenuated infection caused by Candida albicans, Pseudomonas aeruginosa, and methicillin-resistant Staphylococcus aureus (MRSA) in a neutrophil depleted murine model by cyclophosphamide [13]. ...
... AHCC was provided from Amino Up Chemical (Sapporo, Japan). Detail of AHCC was described previously [8][9][10][11][12][13][14][15][16][17]. Infected mice were supplied with 1,000 mg/kg/day of AHCC by oral administration until euthanasia. ...
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Introduction: Pulmonary Mycobacterium avium disease is a chronic and progressive disease that is known to be difficult to treat. Active hexose correlated compound (AHCC) is an extract obtained by culturing mycelia of Basidiomycota. AHCC is reported to attenuate several experimental animal infection models. We hypothesized that AHCC could attenuate pulmonary M. avium disease in mice. Methods: Mycobacterium avium (108 cfu/head) was administered intratracheally into mice (C57/BL6). Infected mice were supplied with 1,000 mg/kg/day of AHCC by oral administration until euthanasia. The mice were sacrificed at seven days later or 21 days later after M. avium infection. The lung homogenates were cultured on Middlebrook 7H10 agar plates for bacterial colony counts. Additionally, the number of inflammatory cells in the lungs was analyzed by FACS. Tissue sections of the lungs were stained by hematoxylin and eosin or Ziehl-Neelsen methods. In addition, the number of bacterial colonies in the macrophages was counted in vitro. Approximately 1x106 macrophages were incubated with M. avium at an MOI of 10 with or without 1 mg/ml of AHCC. Results: The administration of AHCC improved lung inflammation caused by M. avium according to the histology results and decreased number of M. avium in the lungs. In the analysis of lung inflammatory cells, the number of TNFR1 cells and NK cells remained unchanged by AHCC administration, however, the number of TNFR2 cells slightly increased. There was no difference in the number of M. avium in macrophages treated with or without AHCC in the in vitro study. Conclusion: AHCC plays a protective role in a murine model of pulmonary M. avium disease.
... Functional food, active hexose correlated compound (AHCC), is an extract prepared from cultured mycelium of a Basidiomycetes mushroom. Recent reports have shown that supplementation with AHCC exerts a general positive effect on the immune system, as well as anti-inflammatory and anti-oxidant effects8910111213. AHCC is a mixture of poly-and oligo-saccharides, amino acids, lipids, minerals, etc., in which oligosaccharides are the major components , comprising approximately 74% of the mixture. ...
... Supplementation studies with AHCC have demonstrated positive effects on immune function in humans and animal models, including decreased tumor formation [1][2][3] ; increased resistance to viral and bacterial infection [4][5][6][7][8][9] ; enhanced natural killer (NK) cell activity 6,10,11 ; increased dendritic cell function 12 ; increased T-cell proliferation, including altered T-cell activity 3,13 ; altered cytokine production 3,5,13,14 ; suppressed dexamethasone-induced thymic apoptosis in rats 15 ; increased nitric oxide release by peritoneal cells 13 ; and antioxidant [16][17][18] and antiinflammatory effects. 19 Clinical effects and safety have been demonstrated in humans with malignancy, 11,[20][21][22][23][24][25][26] as well as in healthy subjects, 12,27,28 most recently in a report investigating the potential application of AHCC as an immune adjuvant in influenza vaccination. ...
Article
Active hexose correlated compound (AHCC) is a fermented mushroom extract that is commercially available and promoted for immune support. This review focuses on safety and efficacy results from human clinical trials that have included subjects with a variety of cancers, as well as healthy populations. Animal data are also briefly discussed in the context of recent human data, with an emphasis on the possible applications of AHCC in promoting resistance to influenza virus infection. Available data suggest that AHCC supplementation clearly affects immune outcomes and immune cell populations— especially natural killer cell activity. Additional human studies are needed, as well as studies to explore the mechanistic rationale for these reported effects.
... Functional food, active hexose correlated compound (AHCC), is an extract prepared from cultured mycelium of a Basidiomycetes mushroom. Recent reports have shown that supplementation with AHCC exerts a general positive effect on the immune system, as well as anti-inflammatory and anti-oxidant effects8910111213. AHCC is a mixture of poly-and oligo-saccharides, amino acids, lipids, minerals, etc., in which oligosaccharides are the major components , comprising approximately 74% of the mixture. ...
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Supplementation of active hexose correlated compound (AHCC) improved the prognosis of postoperative hepatocellular carcinoma patients. Excess production of nitric oxide (NO) by inducible NO synthase (iNOS) is an inflammatory biomarker in liver injury. AHCC suppressed iNOS induction in hepatocytes, suggesting that AHCC has a potential liver-protective effect. However, the active component in AHCC responsible for NO suppressive activities has not been identified. The objective of this study was to identify this NO suppressive component and to investigate its mechanisms of action. AHCC was subjected to fractionation by cation exchanger, size exclusion chromatography, and normal- and reversed-phase HPLC. Aliquots of the fractions were added to primary cultured rat hepatocytes stimulated with interleukin (IL)-1β, and NO production was assayed. By activity-guided fractionation and electron spray ionization mass spectrometry analysis, adenosine was identified as one of the NO suppressive components in AHCC. Adenosine inhibited NO production, and reduced the expression of iNOS protein and mRNA. It had no effects on IκB degradation, but it inhibited NF-κB activation. Adenosine also inhibited the upregulation of type I IL-1 receptor (IL-1RI). Experiments with iNOS promoter-luciferase constructs revealed that adenosine decreased the levels of iNOS mRNA at the promoter transactivation and mRNA stabilization steps. Adenosine decreased the expression of the iNOS gene antisense transcript, which is involved in iNOS mRNA stability. Adenosine in AHCC suppressed iNOS induction by blocking NF-κB activation and the upregulation of the IL-1RI pathways, resulting in the inhibition of NO production.
... 30 The potential effects of AHCC supplementation against infection with H5N1 avian influenza virus were evaluated in young (6-8-week-old) female BALB/c mice. 16 Mice received AHCC at a dose of 0.5 g/kg body weight/d or an equal volume of phosphate buffer solution (PBS) by gavage for 7 days. At 21 or 28 days posttreatment, mice were infected i.n. with 100 times the 50% lethal dose (LD50) of H5N1 avian influenza virus. ...
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Active hexose correlated compound (AHCC) is a fermented mushroom extract that is promoted for immune support. This review focuses on results from in vivo studies evaluating the effects of AHCC supplementation on survival and the immune response to a variety of infectious agents, including influenza virus, avian influenza virus, Klebsiella pneumoniae, Candida albicans, Pseudomonas aeruginosa, and methicillin-resistant Staphylococcus aureus. Supplementation with AHCC appears to modulate immunity and increase survival in response to acute infection and warrants further investigation.
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An evidence-based systematic review of active hexose correlated compound (AHCC) by the Natural Standard Research Collaboration consolidates the safety and efficacy data available in the scientific literature using a validated, reproducible grading rationale. This article includes written and statistical analysis of clinical trials, plus a compilation of expert opinion, folkloric precedent, history, pharmacology, kinetics/dynamics, interactions, adverse effects, toxicology, and dosing.
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Excess production of nitric oxide (NO) by inducible nitric oxide synthase (iNOS) has been implicated as proinflammatory biomarker in liver injury. The application of active hexose correlated compound (AHCC) as a functional food in complementary and alternative medicine has increased. The possibility that AHCC might inhibit iNOS induction was investigated as a potential liver-protective effect. Hepatocytes were isolated from rats by collagenase perfusion and cultured. Primary cultured hepatocytes were treated with interleukin-1β in the presence or absence of AHCC-sugar fraction (AHCC-SF). AHCC-SF inhibited the production of NO and reduced expressions of iNOS mRNA and its protein. AHCC-SF had no effects on either IκB degradation or nuclear factor-κB (NF-κB) activation. In contrast, AHCC-SF inhibited the upregulation of type I interleukin-1 receptor (IL-1RI) through the inhibition of Akt phosphorylation. Transfection experiments with iNOS promoter-luciferase constructs revealed that AHCC-SF reduced the levels of iNOS mRNA at both promoter transactivation and mRNA stabilization steps. AHCC-SF inhibited the expression of iNOS gene antisense transcript, which is involved in iNOS mRNA stabilization. These findings demonstrate that AHCC-SF suppresses iNOS gene expression through a IκB/NF-κB-independent but Akt/IL-1RI-dependent pathway, resulting in the reduction of NO production. AHCC-SF may have therapeutic potential for various liver injuries.
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