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Beneficial effects of active hexose correlated compound (AHCC) on immobilization stress in the rat
Abstract
Active Hexose Correlated Compound (AHCCTM), an extract from several basidiomycetes, has been known as a biological response modifier (BRM) in humans as well as in animals. In the present study, AHCC was tested for its ability to modulate the hormonal responses to immobilization stress in the rat. AHCC at 3% in drinking water was given to male Wistar rats for one week, then rats were exposed to immobilization for 1 h. At 1 h after immobilization, the serum levels of corticosterone, norepinephrine, epinephrine, dopamine and glucose were increased significantly. Except for the corticosterone levels, all of these changes were restored to control levels by the AHCC pretreatment. These results suggest that AHCC can protect various effects induced by immobilization by attenuating the sympathetic nerve activity.
... [17][18][19] Furthermore, AHCC ® has been shown to stabilize circulating levels of norepinephrine, epinephrine, dopamine, and glucose in rats subjected to immobilized stress, and has also been shown to relieve severe anxiety in patients with unresectable prostate cancer. 20,21 Collectively, these studies suggest that AHCC ® might comprehensively improve the activity of the ANS, endocrine system, and immune system in humans, and be an effective treatment for stress. The present study was conducted to investigate the effects of AHCC ® in healthy volunteers under temporary physical and mental stress condition as well as at rest. ...
AHCC® is a functional food from the basidiomycete Lentinula edodes. We evaluated the effects of AHCC® on subjects under different kinds of stress and at rest. Physical stress was imposed using an active standing test, known as Schellong’s test. Sympathetic nervous activity in the standing position was significantly greater in AHCC®-treated subjects than in a placebo group. In contrast, AHCC® significantly increased parasympathetic nervous activity at rest. Under mental stress, AHCC® increased sympathetic nervous activity, with no difference in the parasympathetic nervous system. In subjects with chronic mental stress, self-reported “initiation and maintenance of sleep” was significantly greater in the AHCC®-intake period than in the placebo intake period, and natural killer cell activity also increased after AHCC® intake, suggesting a possible mechanism of action of AHCC®. Our findings indicate that AHCC® is potentially effective in stress management and may be useful in the treatment of depression.
... However, there are also conflicting appearing MOAs (effects on decreasing oxidative stress, inflammation, and iNOS activity) that suggest require further investigation. 4,[29][30][31][32][33] It is possible that components of AHCC (besides α-1,4-glucans) may be responsible for these effects; however, this is not known. In addition, whether minor variations in production 9 affect the biological activity of this compound is not known. ...
The purpose of this review is to present the currently published evidence regarding the use, efficacy, potential mechanisms of action, and results of published clinical trials regarding the use of a Lentinula edodes mushroom-derived extract (active hexose correlated compound) as complementary therapy in patients with cancer. The authors explore the current preclinical and clinical evidence as it relates to this topic and its potential use in the surgical oncology patient. There has been a growing interest in stimulation of the immune system in trauma, cancer, and surgical patients in general. Little, however, has been written about some-of the supplements in widely used in Japan and China, but relatively unheard of in the United States.
... Although the mechanism of action remains unknown, supplementation studies with AHCC have demonstrated positive effects on various parameters of immune function in both rodents [1][2][3][4][5][6] and humans [7][8][9]. Importantly, the results from several studies using in vivo models have demonstrated increased survival in AHCC-supplemented mice in response to a broad spectrum of acute infections. ...
Supplementation with mushroom-derived active hexose correlated compound (AHCC) modulates immunity and increases survival in response to a broad spectrum of acute infections, including influenza virus infection. However, dose-response data are nonexistent. Therefore, the aims of this study were to evaluate AHCC supplementation at various doses and determine the effects of low-dose supplementation on the immune response in a mouse model of influenza virus infection. We hypothesized that AHCC supplementation would influence the immune response to influenza infection in a dose-dependent manner. Male C57BL/6 mice were supplemented with AHCC at daily doses of 0.05, 0.1, 0.5, and 1 g/kg and infected intranasally with influenza A virus (H1N1, PR8). Supplemented mice demonstrated a dose-dependent increase in survival and reduction in the loss of body weight. To further evaluate the effects of low-dose AHCC supplementation on the immune response to influenza infection, mice were supplemented with 0.1 g/kg per day and infected with a sublethal dose of influenza virus. Supplemented mice exhibited enhanced virus clearance and decreased weight loss compared to controls. Low-dose supplementation did not influence total natural killer (NK) cell cytotoxicity, although lytic efficiency was increased in the spleens of AHCC-supplemented mice, indicating enhanced NK cell function per cell. In conclusion, these data suggest that the effects of AHCC on the immune response to influenza infection are dose dependent and that low-dose AHCC supplementation improves the response to influenza infection despite no effect on total NK cell cytotoxicity.
... These oligosaccharides are believed to account for the biological activities of AHCC. Supplementation with AHCC has shown a generalized positive effect on the immune systems of both rodents (10)(11)(12)(13)(14) and humans (15,16), as well as antioxidant effects (17,18), and is well-tolerated by both rodents and humans, with no reported adverse effects. Studies to date have suggested that AHCC may increase NK activity in humans (16) and rodents (11,14) with malignancies. ...
The emergence of H5N1 avian influenza and the threat of new or adapted viruses in bioterrorism have created an urgent interest in identifying agents to enhance the immune response to primary virus infection. Active hexose correlated compound (AHCC) is a natural mushroom extract reported to increase natural killer (NK) cell activity, survival, and bacterial clearance in young mice. However, the effects of AHCC on the response to viral infections have not been studied. In this study, young C57BL/6 mice were supplemented with 1 g AHCC/(kg body weight x d) for 1 wk prior to and throughout infection with influenza A (H1N1, PR8). Supplementation increased survival, decreased the severity of infection, and shortened recovery time following intranasal infection with flu, as determined by the recovery of body weight and epithelial integrity in the lungs. AHCC increased NK activity in lungs at d 1 (P < 0.05) and d 4 (P < 0.01) and in the spleen at d 2 postinfection (P < 0.01). Supplementation increased the percentage (P < 0.05) and number (P < 0.01) of NK1.1+ cells in the lung and reduced the infiltration of lymphocytes and macrophages compared with controls (P < 0.01). These data suggest that AHCC supplementation boosts NK activity, improves survival, and reduces the severity of influenza infection in young mice. Bolstering innate immunity with dietary bioactives may be one avenue for improving the immune response to primary flu infection.
... Proof of this postulate will require additional experi- mentation. Active hexose correlated compound may be taken as a nutritional supplement212223242526272829303132333435. Therefore, it is possible that the direct effects of AHCC on the nutritional status of the host contributed to the enhanced resistance to infection of the food-deprived and infected mice. ...
Infection is the most common postoperative complication within the surgical wound and during severe trauma. In spite of the use of modern sterile techniques and prophylaxis, infection continues to be a leading cause of death in these patients. Therefore, it has become crucial to develop new alternatives to prevent the effects of trauma and other complications on the immune system and improve resistance to infection. The objective of this study was to test the prophylactic effects of oral administration of active hexose correlated compound (AHCC), a natural immunoenhancer, on survival in a mouse model of surgical soft tissue infection.
The model involves the intramuscular administration of a 50% lethal dose (LD50) of K. pneumoniae to mice that have restricted food intake for 24 hours prior to and six hours after infection and simulates local infection and food deprivation that often occur during trauma or surgical procedures. In the present study, AHCC was administrated orally to Swiss Webster mice for eight days prior to and during the infection period. Survival, time of death, LD50, and clearance of bacteria of this group were compared with those control mice receiving the excipient alone.
Survival and mean time to death were increased significantly in the AHCC-treated group; the LD50 was greater in mice receiving AHCC than in mice receiving the excipient. Mice receiving AHCC were better able to clear bacteria from their systems than were control animals.
The results suggest that AHCC protects mice in this model by restoring the immune and other systems negatively affected by trauma, infection, and food deprivation. More studies are necessary to determine the intrinsic mechanisms involved in this model and whether AHCC can prevent infection or improve survival in human beings with severe trauma or undergoing surgical procedures.
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.
Includes abstract and vita. Thesis (Ph.D.)--Drexel University, 2007. Includes bibliographical references (leaves 184-200).
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.
Active hexose correlated compound (AHCC), an extract derived from fungi of Basidiomycetes family, has been found to be a potent antioxidant. Since the secretion of some hormones can be affected by reactive oxygen species, the objective of this study was to examine how ferric nitrilotriacetate (FeNTA), which generates hydroxyl radicals in vivo, modulates the hormone secretion and the effects of AHCC.
AHCC at 3 % in drinking water was given to male rats for one week, and the animals were decapitated at different time intervals after the treatment with FeNTA intraperitoneally. Serum levels of hormones (corticosterone, testosterone, thyroxine and triiodothyronine), adrenal ascorbic acid as well as changes in hepatic oxidative status were evaluated by immunoassay and spectrometry.
Serum corticosterone levels increased significantly following FeNTA treatment, while AHCC reduced the increased levels to normal. Adrenal ascorbic acid levels that reflect ACTH secretion, were decreased by FeNTA and restored to normal by AHCC. Serum levels of testosterone and thyroxine (T4) decreased rapidly after FeNTA treatment, while AHCC pretreatment prevented this fall. Serum triiodothyroxine (T3) levels remained unchanged either by FeNTA or AHCC treatment. The hepatic oxidized glutathione, glutathione-related enzymes and also serum lipid peroxide were greatly enhanced after FeNTA treatment. All of these changes were restored to normal by AHCC pretreatment.
FeNTA induces various endocrine disorders and AHCC ameliorates these effects by acting as an antioxidant.
Infection is a serious, costly, and common complication of surgery and constitutes the principal cause of late death in patients undergoing surgery. The objective of this study was to clarify the mechanisms by which active hexose correlated compound (AHCC) increases survival in a murine model of intramuscular infection.
Food-deprived mice receiving either AHCC or excipient were infected with bacteria. Kinetics of bacterial load, white blood cell counts, cytokine levels, and antibody levels were compared between groups.
AHCC-treated mice had reduced bacterial load at day 5 and cleared bacteria entirely at day 6. Levels of interleukin-12, tumor necrosis factor-alpha, and interleukin-6 peaked earlier in this group (day 3) compared with controls (day 5). Increased percentages of peripheral lymphocytes and monocytes and decreased numbers of polymorphonuclear cells were detected in the AHCC group.
AHCC appears to induce an early activation of the immune response, leading to an effective clearance of bacteria and rapid recovery.
Hormone-metabolite interrelationships were investigated in 21 burned subjects. Patients showed raised blood concentrations of glucose, the gluconeogenic substrates, lactate, pyruvate, alanine and glycerol, and hypertriglyceridaemia. Plasma cortisol levels were raised especially in the early stage. Plasma glucagon levels were high with peak values 3–4 days after the initial injury, while insulin levels were inappropriately low. The extent of these metabolic changes correlated with the extent of injury. Plasma cortisol showed strong correlations over the first 5 days with blood alanine, lactate, total gluconeogenic substrates, plasma NEFA (non-esterified fatty acids) and blood total ketone bodies, whereas the correlations for glucagon, if present, were much weaker. Conversely there were strong negative correlations between insulin and plasma NEFA, blood glycerol and total ketone bodies; similar correlations were noted for the [insulin]: [glucagon] molar ratio.The data suggest the important roles of elevated cortisol levels and insulin insufficiency in the metabolic response to burn injury.
The potential involvement of the sympathoadrenal system in stress-induced secretion of peptides from the intermediate lobe of the pituitary gland and the activation of the pituitary-adrenal axis was studied. Male Wistar rats were subjected to control procedures, to sympathectomy by chronic administration (8 weeks) of guanethidine and/or to medullectomy by adrenal enucleation 9 weeks prior to exposure to forced immobilization stress for various periods of time. In intact or sham-operated rats, immobilization caused a prompt increase of circulating norepinephrine, epinephrine (EPI), corticosterone and of immunoreactive adrenocorticotropic hormone (ACTHi), α-melanocyte-stimulating hormone (α-MSHi) and β-endorphin (β-ENDi). Peak levels of pituitary hormones were found after 10 min of stress exposure, but fell to less than 30% of these levels after 2.5 h of immobilization. Adrenal medullectomy, which abolished the stress-induced release of EPI, reduced the acute increase of plasma α-MSHi and β-ENDi, but dit not influence the acute increase of plasma ACTHi during immobilization stress. Also in medullectomized plus sympathectomized rats, the initial stress response of circulating ACTHi was not different from that of controls. Adrenal medullectomy with or without additional sympathectomy caused a marked increase in plasma ACTHi concentrations after prolonged stress exposure. We conclude that: (1) catecholamines originating from the adrenalmedulla facilitate the stress-induced secretion of intermediate lobe peptides (α-MSHi, β-ENDi); (2) catecholamines from the sympathoadrenomedullary system do not contribute to the acute release of ACTH during immobilization stress; (3) the sympathoadrenomedullary system is involved in the secondary reduction of circulating ACTHi levels seen during prolonged stress.
Rates of glucose and of lactate production, and of gluconeogenesis from lactate were measured in unanaesthetized dogs with indwelling arterial and venous catheters. 2-t-glucose, l(+)-lactate-14C, or the mixture of the two were used as tracers according to the primed, constant infusion technique. Norepinephrine infusion had virtually no effect on carbohydrate metabolism. In the normal dog, epinephrine caused increases in plasma glucose levels (about 50%) and in glucose production (35%); lactate turnover increased nearly fourfold, and gluconeogenesis from lactate increased proportionally, thereby almost tripling the lactate contribution to glucose production. There was a logarithmic correlation between plasma lactate level and lactate turnover and a straight line correlation between lactate turnover and the rate of formation of glucose from lactate. The increase of lactate turnover after lactate infusion alone, and combined with norepinephrine, and after methylprednisolone treatment fitted the straight line correlation. It was therefore concluded that in vivo the lactate mobilization limits gluconeogenesis from this source. methylprednisolone pretreatment greatly potentiated the effect of epinephrine. Plasma glucose was increased to . Glucose production rose to four to eight times normal, and gluconeogenesis from lactate rose to eight to ten times the normal values.
The purpose of the present study was to analyze the influence of stress (24-h cold exposure) on presynaptic 5-HT1A receptors, and on postsynaptic 5-HT1A, 5-HT1C and 5-HT2 receptors. Cold exposure for 24 h affected neither pargyline-induced decreases in 5-hydroxyindoleacetic acid (5-HIAA) levels in midbrain and rest of brain, nor plasma glucose and corticosterone levels. Treatment with the 5-HT1A receptor agonist, 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT; 0.5-1 mg/kg), 3-5 h after the end of cold exposure triggered less intense flat body posture and forepaw treading in cold-exposed rats than in controls. On the other hand, 15- and 30-min plasma glucose responses to 8-OH-DPAT (0.25-0.5 mg/kg, 3-5 h after cold) or to the alpha 2-adrenoceptor agonist, clonidine (0.025 mg/kg), were not affected by cold, while the 15-min, but not the 30 min, plasma corticosterone response to 8-OH-DPAT was slightly amplified in cold-exposed rats. Cold exposure affected neither the inhibitory effect of 8-OH-DPAT (0.25-0.5 mg/kg, 3-5 h after cold) on midbrain 5-HIAA levels, nor the hypothermic effect of 8-OH-DPAT (0.5-1 mg/kg, 3-5 h after cold). Lastly, the hypoactivity elicited by the 5-HT1C receptor agonist, m-chlorophenyl-piperazine (1.5-3 mg/kg, 3-5 h after cold), or head shakes elicited by the 5-HT2 receptor agonist, 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (1-2 mg/kg, 3-5 h after cold), were of similar intensities in control and in cold-exposed rats.
The aim of this study was to investigate whether 5-HT1A receptor-mediated adrenal catecholamine release undergoes rapid desensitisation. Thus, we measured plasma adrenaline either following the acute administration of the 5-HT1A receptor agonist, 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT, 0.3 mg/kg i.v.), or during immobilisation stress, in rats pretreated repeatedly with saline or with the 5-HT1A receptor agonist, ipsapirone (10 mg/kg i.p., t.i.d. for 7 days). Plasma corticosterone and glucose were measured concomitantly. Neither body weight nor basal plasma adrenaline and corticosterone levels were significantly affected by ipsapirone treatment. Conversely, the latter diminished basal plasma glucose levels. While the 8-OH-DPAT-induced elevations in plasma adrenaline remained unaffected by ipsapirone, the 8-OH-DPAT-induced elevations in plasma corticosterone and glucose tended to be diminished by ipsapirone. Ipsapirone treatment modified the kinetics, but not the amount of adrenaline released by stress. On the other hand, stress-induced activation of the corticotropic axis was amplified by ipsapirone. Lastly, ipsapirone treatment again tended to diminish the hyperglycemic response to stress. These results indicate that (i) 5-HT1A receptor-mediated activation of adrenaline release is not desensitised by short-term ipsapirone treatment, (ii) the anxiolytic/antidepressant effect of ipsapirone may not be explainable in terms of tolerance to some neuroendorinological consequences of stress.
The effect of immobilization stress was studied in rats in which the CRF and arginine vasopressin-containing innervation of the median eminence was destroyed by an anterolateral cut (ALC) around the medial basal hypothalamus. One week after surgery, the rats with ALC were subjected to immobilization and they showed a normal rise in plasma corticosterone, a smaller than normal rise of plasma ACTH, and an increased response of plasma epinephrine and norepinephrine. When in rats with an ALC the response of plasma catecholamines was prevented by guanethidine pretreatment and adrenal enucleation the small rise in plasma ACTH was unchanged during immobilization. In addition, the plasma corticosterone and ACTH rises during immobilization in the rats with ALC were not influenced by prior treatment with phentolamine (2.5 mg/kg ip) or propranolol (2.5 mg/kg ip). These findings suggest that the large rises in plasma epinephrine and norepinephrine levels during immobilization do not contribute to changes in plasma ACTH or corticosterone levels when hypothalamic regulation via CRF and/or arginine vasopressin is interrupted by ALC.
Norepinephrine and dopamine, which were assayed by means of a sensitive enzymatic isotopic method, were found to be unevenly distributed among the areas which make up the limbic system. Both catecholamines could be detected in all of the regions studied. Many regions of the limbic system were richly endowed with one or both of these compounds. The concentration of norepinephrine was particularly high in the dorsal part of the nucleus interstitialis striae terminalis, the nucleus interstitialis striae medullaris, and the nucleus tractus diagonalis; the concentration of dopamine was very high in the olfactory tubercle and in the area amygdaloidea anterior.
Immobilization stress in rats is accompanied by a fast and transient increase in plasma catecholamines (CA) and a slow but more sustained increase in plasma corticosterone (CORT) levels. CA are reported to increase prostacyclin (PGI2) secretion in endothelial cells in culture and in isolated vascular tissue. The present study was undertaken to determine a) whether short term immobilization stress in rats affects PGI2 synthesis in aortic tissue and b) whether such effects are dependent on the maintenance of an intact hypothalamic-pituitary-adrenal axis. Male Sprague Dawley rats were immobilized for 5, 15 and 30 min., killed by a blow to the head and aortic rings immediately prepared and incubated in oxygenated Krebs-Ringer buffer at 37 degrees C. Secretion of PGI2 was assessed by measuring the amount of 6-keto-PGF1 alpha, the stable hydrolysis product of PGI2, formed in the incubation medium during 90 min. Rats immobilized for 15 min demonstrated a six to seven times increase in plasma ACTH and a more than ten times increase in plasma CORT levels. Aortic rings from stressed rats also demonstrated a significant and sustained (2 hours) increase in PGI2 secretion when compared with tissue from unstressed rats (68 pg 6-keto-PGF1 alpha/mg tissue per min vs 35 pg 6-keto-PGF1 alpha/mg tissue per min during the first hour). Shorter (5 min) or longer (30 min) periods of stress gave comparable results. Adrenalectomy (ADX) carried out 7 days prior to immobilization, did not affect the baseline secretion of the eicosanoid, but completely prevented the increase in PGI2 by immobilization stress. Administration of 2 micrograms/kg and 200 micrograms/kg i.a. of CORT to ADX-rats produced plasma levels of the hormone (36 +/- 12 ng/ml and 934 +/- 366 ng/ml respectively) comparable to those seen in unstressed and stressed rats. However only the higher dose of CORT when administered immediately prior to stress, restored the effect of immobilization stress on PGI2 synthesis in aortic tissue of ADX-rats. Administration of the protein synthesis inhibitor cycloheximide (1 mg/kg) prior to stress did not affect the increase in PGI2 secretion. In contrast to restraint stress, co-administration of ACTH and NE which also raised plasma levels of ACTH, CORT and NE to peak stress levels, did not increase prostacyclin production in aortic tissue. In conclusion, our findings demonstrate that short periods of immobilization stress produce a rapid and sustained increase in PGI2 synthesis in the rat aorta, provided plasma levels of CORT are elevated.(ABSTRACT TRUNCATED AT 400 WORDS)