Oral administration of active hexose correlated compound enhances host resistance to West Nile encephalitis in mice.

West Nile virus (WNV) poses a serious threat to public health, especially to the elderly and the immuno-compromised. Neither vaccines nor treatments are available for humans. Active hexose correlated compound (AHCC) is an extract of Lentinula edodes of the Basidiomycete family of fungi rich in alpha-glucans. In this study, we evaluated the effect of AHCC on host susceptibility in the murine model of WNV infection. Mice orally administered with AHCC (600 mg/kg) every other day for 1 wk before and at d 1 and 3 postinfection were assessed using viremia levels, survival rate, and protective immunity. AHCC administration in young (6- to 8-wk-old) mice attenuated viremia and mortality following lethal WNV infection. WNV-specific IgM and IgG production and gammadelta T cell expansion were also enhanced in these mice. Aged (21- to 22-mo-old) mice were more susceptible to WNV infection than young mice, partially due to the dysfunction of gammadelta T cell subsets. AHCC administration in aged mice enhanced the protective Vgamma1(+) T cell response as well as WNV-specific IgG but not IgM antibodies production. AHCC administration in aged mice attenuated viremia levels but led to no difference in mortality rate. Overall, our data suggests that AHCC enhances protective host immune responses against WNV infection in young and aged mice. Dietary supplementation with AHCC may be potentially immunotherapeutic for WNV-susceptible populations.

Oligonol inhibits UVB-induced COX-2 expression in HR-1 hairless mouse skin--AP-1 and C/EBP as potential upstream targets.

Oxidative stress and inflammatory tissue damage are two major events frequently implicated in carcinogenesis. Numerous polyphenolic compounds derived from plants possess antioxidant and anti-inflammatory activities and are hence effective in preventing cancer. Oligonol is a polyphenol formulation enriched with catechin-type oligomers. As an initial approach to assess the chemopreventive potential of oligonol, we have determined its effects on inflammatory as well as oxidative damage in mouse skin irradiated with UVB. Topical application of oligonol onto the dorsal skin of male HR-1 hairless mice 30 min prior to UVB exposure diminished epidermal hyperplasia and formation of 4-hydroxynonenal, a biochemical hallmark of lipid peroxidation. Topical application of oligonol also significantly inhibited UVB-induced cyclooxygenase (COX-2) expression in mouse skin. Oligonol diminished the DNA binding of activator protein-1 (AP-1) and CCAAT/enhancer binding protein (C/EBP), and the expression of C/EBPdelta in mouse skin exposed to UVB. Our study also revealed that oligonol attenuated UVB-induced catalytic activity as well as expression of p38 mitogen-activated protein (MAP) kinase. Moreover, UVB-induced phosphorylation of another upstream kinase Akt was attenuated by oligonol. Taken together, oligonol showed antioxidative and anti-inflammatory effects in UVB-irradiated mouse skin by inhibiting COX-2 expression via blockade of the activation of AP-1 and C/EBP, and upstream kinases including p38 MAP kinase and Akt.

Modulation of infection-induced inflammation and locomotive deficit and longevity in senescence-accelerated mice-prone (SAMP8) model by the oligomerized polyphenol Oligonol.

Oligonol is produced from the oligomerization of polyphenols (typically proanthocyanidin from a variety of fruits such as lychees, grapes, apples, persimmons, etc.) and contains catechin-type monomers and oligomers of proanthocyanidins. The ability of Oligonol to affect infection-dependent eye inflammation, locomotion and longevity in senescence-accelerated prone mice (SAMP8) (a model of senescence acceleration and geriatric disorders with increased oxidative stress and neuronal deficit) was investigated. Oligonol (60mg/kg) significantly modulated the extent of inflammation scores in the eye of SAMP8 mice. Examination of the mice indicated infection with mouse hepatitis virus and pinworm (Syphacia obvelata) in both males and females and with the intestinal protozoa (trichomonad) in males. A comparison of the two groups (using log-rank test) and the difference in the mean life span between groups (using Student's t-test) indicated significant differences in survival (p=0.043) and the mean life span (p=0.033) in male SAMP8 mice. Oligonol increased the mean life span and this was statistically significant. In the open-field locomotive test, the 7-week-old SAMP8 mice crossed more than 40 partitioned lines in 1min. At 48-week-old control untreated male SAMP8 crossed 2 lines. The Oligonol-treated 48-week-old male SAMP8 mice crossed 17 lines however. The improved locomotive activity was statistically significant even after 36weeks in the Oligonol-treated male SAMP8 but this was not the case throughout the time course of the study in the Oligonol-treated female SAMP8. Thus Oligonol treatment to SAMP8 mice modulated the severity of infection-dependent inflammation, prolonged life-span and significantly improved locomotive activity indicating potential benefit to aging-associated diseases such as Alzheimer's or Parkinson's diseases. This presents potential for further research to define infection-dependent inflammation associated with degenerative conditions and the molecular mechanism of dietary antioxidant protection.

Preparation, characterization, and antioxidative effects of oligomeric proanthocyanidin-L-cysteine complexes.

Controlled acid-catalyzed degradation of proanthocyanidin polymers in grape seeds together with L-cysteine led to oligomeric proanthocyanidin-L-cysteine complexes along with monomeric flavan-3-ol derivatives being isolated, and their structures were confirmed on the basis of spectroscopic data and by chemical means. In addition, comparative studies on the antioxidative and survival effects of oligomeric proanthocyanidin-L-cysteine complexes and proanthocyanidin polymers were performed. The oligomeric proanthocyanidin-L-cysteine complexes showed higher bioavailability and antioxidant capacity and enhanced survival time in the animal test groups. In addition, it is suggested that the oligomeric complexes may help to prevent oxidative stress and may reduce free radical production.

Evaluation of the safety and toxicity of the oligomerized polyphenol Oligonol.

Oligonol((R)) is an optimised phenolic product containing catechin-type monomers and lower oligomers of proanthocyanidin that emanate from a technology process which converts polyphenol polymers into oligomers. In a single dose toxicity study administration of Oligonol (2000mg/kg bw) by gavage for 4 weeks was found to be safe with no side effects (such as abnormal behavior and alopecia). Body weight gain and food consumption were within normal range. Oligonol had no observed toxicity at the dose (1/25 of LD(50)) administered for 6 months. This suggests that Oligonol is safe at repeated human intakes of Oligonol in doses lower than 200mg/day. The highest dose used in this study is equal to 12g daily for an adult man with 60kg body weight. The LD(50) was calculated to be 5.0g/kg body weight (95% confidence limit: 3.5-6.4g/kg). Studies conducted on 30 healthy volunteers consuming Oligonol at doses of 100mg/day and 200mg/day for 92 days showed good bioavailability. The biochemical parameters attesting to liver and kidney functions as well as the hematological parameters were within the normal ranges. The potential of Oligonol to induce gene mutation (a reverse mutation test) was tested using Salmonella typhimurium TA98, TA100, TA104, TA1535, TA153 and Escherichia coli WP2uvrA. Oligonol was not mutagenic to the tester strains. The lack of toxicity supports the potential use of Oligonol as a food or dietary supplement and for use as an additive in pharmaceutical and cosmetological applications.

Platelet reactivity in male smokers following the acute consumption of a flavanol-rich grapeseed extract.

Epidemiological studies suggest that a high dietary intake of flavanols, a subclass of flavonoids, is associated with reduced risk of vascular disease. Clinical studies have also shown that the consumption of certain flavanol-rich foods (e.g., cocoa, tea, red wine), as well as intake of the individual flavanol (-)-epicatechin, can result in improvement in a number of parameters associated with vascular disease, including improved endothelial function, reduced platelet reactivity, and reduced oxidative stress. The present study assessed the effects of a flavanol-rich supplement on platelet reactivity and plasma oxidant defense in a group of smokers, a population at an elevated risk for vascular disease. Male smokers were randomly assigned to a placebo (n = 10) or a flavanol-rich grapeseed extract (FRGSE; n = 13) group, and after an overnight fast, blood samples were collected before and at 1, 2, and 6 hours following consumption of the placebo or supplement. The FRGSE supplement, but not the placebo, significantly decreased ADP-stimulated platelet reactivity at 1, 2, and 6 hours following intake (P < .05) compared to baseline levels. Similarly, the supplement, but not the placebo, decreased epinephrine-stimulated platelet reactivity 2 hours following consumption. Plasma antioxidant capacity (total radical trapping antioxidant potential), lipid oxidation (plasma thiobarbituric acid-reactive substances), and serum uric acid concentrations were not affected in either group. Thus smokers may obtain some health benefits from the consumption of certain flavanol-rich foods, beverages, and supplements.

A Phase I study of the safety of the nutritional supplement, active hexose correlated compound, AHCC, in healthy volunteers.

Active Hexose Correlated Compound (AHCC) is an extract of Lentinula edodes of the basidiomycete family of fungi rich in alpha glucans. AHCC has been used for many years as a dietary supplement to enhance the immune system and in clinical trials as an adjunctive treatment in Hepatocellular cancer. This multiple dose, Phase I trial, using FDA guidelines, directly investigates the clinical safety and tolerability of AHCC in healthy subjects. Its safety has been based previously on anecdotal reports and its use in clinical practice. Twenty-six healthy male or female subjects between the ages of 18 and 61 were recruited from the community and gave their consent to participate in the trial. The subjects were given 9 g of AHCC (150 mL of the currently available liquid AHCC) PO daily for 14 d. Laboratory data was obtained at baseline and after 14 d of exposure to AHCC and adverse events were monitored by a non-directed review of systems questionnaire three times during the trial. At each visit the vital signs and adverse events were recorded. Two subjects (7%) dropped out because of nausea and intolerance of the liquid. Adverse effects of nausea, diarrhea, bloating, headache, fatigue, and foot cramps occurred in a total of 6 subjects (20%) but were mild and transient. There were no laboratory abnormalities. When used in high dose in healthy subjects, AHCC causes no significant abnormality in laboratory parameters. The adverse effects of 9 g of liquid AHCC per day, a higher dose than used in routine clinical applications, are minimal and the dose was tolerated by 85% of the subjects.

Comparative efficacy of oligonol, catechin and (-)-epigallocatechin 3-O-gallate in modulating the potassium bromate-induced renal toxicity in rats.

Potassium bromate (KBrO(3)) is a by-product from ozonation of high-bromide surface water for production of drinking water and is a rodent carcinogen. Oligonol is a product emanating from the oligomerization of polyphenols, typically proanthocyanidin from a variety of fruits (grapes, apples, persimmons, etc.) and contains catechin-type monomers and proanthocyanidin oligomers. In this study, the ability of oligonol derived from grape seeds, grape seeds extracts (Product A, containing biologically active flavonoids and the oligomeric proanthocyanidin) and pine bark extracts (Product B, composed of flavan-3-ol derivatives) to modulate the KBrO(3)-induced renal toxicity was compared with (+) catechin and (-)-epigallocatechin 3-O-gallate (EGCG). In the Trolox equivalent antioxidant capacity (TEAC) assay, the order of the antioxidant activity was EGCG>catechin>oligonol>Product A>Product B. However, oligonol elicits the strongest antioxidant capacity following in vivo supplementation to rats, with the order of efficacy of oligonol>Product A> or =Product B>EGCG>catechin. Blood levels of lipid peroxidation products (LPO), urea nitrogen (BUN) and creatinine were elevated by KBrO(3) treatment. Oligonol significantly restored LPO to the level in the untreated rats and had the strongest potency when compared with the effects of Products A and B. The five materials lowered KBrO(3)-induced BUN level, but this was not statistically significant. Oligonol significantly reduced the increased level of the creatinine, seconded by Product A, Product B and EGCG. Catechin had the lowest effect in both the BUN and creatinine levels. That oligonol was able to modulate KBrO(3)-induced lipid peroxidation and the levels of blood urea nitrogen and creatinine suggests potential chemopreventive function and application in mitigating toxicity due to long-term exposure to KBrO(3) in public drinking water.

Active hexose correlated compound (AHCC) enhances resistance to infection in a mouse model of surgical wound infection.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Low molecular proanthocyanidin dietary biofactor Oligonol: Its modulation of oxidative stress, bioefficacy, neuroprotection, food application and chemoprevention potentials.

Interdisciplinary research endeavors are directed at understanding the molecular mechanisms of neurodegenerative and chronic diseases that affect human lifestyle. Hence the potential for developing medicinal herb-derived and food plant-derived prophylactic agents directed at neurological, metabolic, cardiovascular and psychiatric disorders abounds. Oligonol is a novel technology product emanating from the oligomerization of polyphenols, typically proanthocyanidin from a variety of fruits (grapes, apples, persimmons etc.) that has optimized bioavailability. It is an optimized phenolic product containing catechin-type monomers and oligomeric proanthocyanidins, the easily absorbed forms. Typically the constituents of Oligonol are 15-20% monomers, 8-12% dimers and 5-10% trimers. Supplementation of mice with Oligonol prior to the administration of ferric-nitrilotriacetic complex (a Fenton chemistry model) significantly reduced the extent of lipid peroxidation in the kidney, brain and liver. Oligonol triggers apoptosis in the MCF-7 and MDA-MB-231 breast cancer cells through modulation of the pro-apoptotic Bcl-2 family of proteins and the MEK/ERK signaling pathway, an observation suggesting its important chemopreventive effects. The senescence-accelerated strain of mice (SAM) are models of senescence acceleration and geriatric disorders which exhibit learning and memory deficits and enhanced production or defective control of oxidative stress leading.

Protective effects of oligomers of grape seed polyphenols against beta-amyloid-induced oxidative cell death.

beta-Amyloid (Abeta) is considered to be responsible for the formation of senile plaques that accumulate in the brains of patients with Alzheimer's disease (AD). There is compelling evidence supporting the notion that Abeta-induced cytotoxicity is mediated through the generation of reactive oxygen species (ROS). Recently, considerable attention has been focused on a wide array of non-vitamin antioxidants present in edible plants that are able to scavenge ROS, thereby protecting against oxidative damage. In this study, we have investigated the possible protective effects of formulated polyphenol oligomers (Oligonol) derived from grape seed extracts on Abeta-induced oxidative cell death. Rat pheochromocytoma (PC12) cells treated with Abeta exhibited increased accumulation of intracellular ROS and underwent apoptosis, as determined by positive in situ terminal end labeling, decreased mitochondrial membrane potential, and the cleavage of poly(ADP-ribose)polymerase. Oligonal attenuated Abeta-induced cytotoxicity, apoptotic features, intracellular ROS accumulation, and lipid peroxidation and increased the cellular glutathione pool. Moreover, Abeta transiently induced the activation of nuclear factor kappaB in PC12 cells, which was suppressed by pretreatment with Oligonol.

The role of beta-glucuronidase in induction of apoptosis by genistein combined polysaccharide (GCP) in xenogeneic mice bearing human mammary cancer cells.

In order to reveal the mechanisms underlying genistein combined polysaccharide (GCP) inhibition of tumor proliferation, we investigated the effects of GCP on the growth of human breast cancer cells transplanted to athymic nude mice. We further investigated the metabolism of genistein and its association with the beta-glucuronidase activity in tumor and normal tissues.

Active hexose correlated compound enhances the immune function of mice in the hindlimb-unloading model of spaceflight conditions.

Hindlimb unloading is a ground-based model that simulates some of the aspects of spaceflight conditions, including lack of load bearing on hindlimbs and a fluid shift to the head. It has been shown that treatment with active hexose correlated compound (AHCC) restores resistance to infection in mice maintained under hindlimb-unloading conditions. The present study was designed to clarify the mechanisms by which AHCC enhances resistance to infection in this model. We hypothesized that oral administration of AHCC will enhance the function of the immune system, which could lead to the increased resistance to infection observed in this model. AHCC or the excipient was orally administered to mice, and the function of the immune system was assessed in spleen and peritoneal cells isolated from those groups. The results of the present study showed that administration of AHCC for 1 wk before and throughout the second day of the hindlimb-unloading period enhanced the function of the immune system assessed by spleen cell proliferation and cytokine production in spleens and nitric oxide and cytokine production in peritoneal cells. These findings suggest that AHCC can be used as a potent immunoenhancer, especially in cases in which the immune system is suppressed by any condition, including diseases such as human immunodeficiency virus infection and cancer.

Active hexose correlated compound enhances resistance to Klebsiella pneumoniae infection in mice in the hindlimb-unloading model of spaceflight conditions.

Previous studies have demonstrated that resistance to infection is decreased in Swiss Webster female mice maintained in the hindlimb-unloading model (Aviles H, Belay T, Fountain K, Vance M, and Sonnenfeld G. J Appl Physiol 95: 73-80, 2003; Belay T, Aviles H, Vance M, Fountain K, and Sonnenfeld G. J Allergy Clin Immunol 110: 262-268, 2002). This is a model of some of the aspects of spaceflight conditions, including lack of load bearing on hindlimbs and a fluid shift to the head. Active hexose correlated compound (AHCC), extracted from Basidiomycete mushrooms, has been shown to induce enhancement of immune responses, including enhanced natural killer activity. In the present study, AHCC was orally administered to mice to determine whether the treatment could decrease immunosuppression and mortality of mice maintained in the hindlimb-unloaded model and infected with Klebsiella pneumoniae. The results of the present study showed that administration of AHCC by gavage for 1 wk (1 g/kg body wt) before suspension and throughout the 10-day suspension period yielded significant beneficial effects for the hindlimb-unloaded group, including 1). decreased mortality, 2). increased time to death, and 3). increased ability to clear bacteria. The results suggest that AHCC can decrease the deleterious effects of the hindlimb-unloading model on immunity and resistance to infection.

Inhibition of human breast cancer growth by GCP (genistein combined polysaccharide) in xenogeneic athymic mice: involvement of genistein biotransformation by beta-glucuronidase from tumor tissues.

The role of beta-glucuronidase in genistein biotransformation was investigated in a human breast cancer MDA-MB-231 xenogeneic athymic mouse model. Genistein combined polysaccharide (GCP), a genistein aglycone rich functional food supplement was used in these experiments. Tumor-bearing mice were subjected to oral administration of GCP for 28 days. GCP treatment significantly inhibited tumor growth. Induction of apoptosis by GCP treatment was related to activation of cleavage of poly(ADP-ribose)polymerase, induction of the p21 protein expression and reduction of cyclin B1 expression in the tumor tissues. Genistein exists as a glucuronide conjugate in normal organ tissues, and the conjugated genistein lacks the physiological activity of the aglycone. Tumor tissues contain large amounts of beta-glucuronidase, the enzyme that converts the genistein beta-glucuronide conjugate into genistein aglycone. The resulting genistein aglycone exerts its chemopreventive activities, including the induction of apoptosis in tumor tissues, and, finally, leads to tumor growth inhibition.

A natural immune modulator attenuates stress hormone and catecholamine concentrations in polymicrobial peritonitis.

BACKGROUND: Activated hexose correlated compound (AHCC), derived from shiitake mushrooms, increases resistance to infection in immunocompromised hosts with positive effects on dendritic cells, natural killer cell function and interleukin 12 production. It may also be attenuating the systemic inflammatory response by regulating the secretion of cortisol and norepinephrine (NE). METHODS: Female Swiss-Weber mice were pretreated with AHCC (Amino Up Chemical Co., Sapporo, Japan) or water by gavage for 10 days before undergoing cecal ligation and puncture (CLP). Peritoneal exudate cells and blood samples were harvested at 4 hours and 24 hours following CLP. Plasma and peritoneal concentrations of cortisol and NE were obtained using enzyme-linked immunosorbent assay. Peritoneal bacteria were quantified by colony counts after 4 hours and 24 hours. Significance was denoted by a p < 0.05. RESULTS: Plasma and peritoneal cortisol concentrations were increased 4 hours after CLP compared with normal controls, with no difference between the pretreated groups. Concentrations of cortisol decreased from 4 hours to 24 hours after CLP with AHCC (plasma, p = 0.009; peritoneal, p < 0.001), and peritoneal cortisol at 24 hours was lower with AHCC as compared with water (p = 0.028). There was no change in plasma or peritoneal NE concentrations at 4 hours. At 24 hours, higher concentrations of NE were detected in both plasma and peritoneal fluid, with lower plasma concentrations in those gavaged with AHCC (p = 0.015). There was no significant difference in peritoneal bacteria counts. CONCLUSION: Enhanced immune function observed with AHCC could be caused by attenuated concentrations of stress hormones and catecholamines.

Lycium barbarum (goji) juice improves in vivo antioxidant biomarkers in serum of healthy adults.

Although Lycium barbarum (goji) and active compounds, Lycium barbarum polysaccharides (LBP), have a high in vitro antioxidant score as determined by simple chemical reaction methods, their in vivo antioxidant effects in humans have not been extensively examined. After our earlier report that an LBP-standardized Lycium barbarum preparation (GoChi) helps prevent oxidant stress-related conditions in humans, our present study examined the hypothesis that the antioxidant effects of GoChi result from its ability to enhance endogenous antioxidant factors. We investigated the effects of GoChi in a 30-day randomized, double-blind, placebo-controlled clinical study. The study population included 50 Chinese healthy adults aged 55 to 72 years. In vivo antioxidant markers, consisting of serum levels of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and lipid peroxidation (indicated by decreased levels of malondialdehyde, MDA) were examined preintervention and postintervention with GoChi or placebo (120 mL/d). In the GoChi group, antioxidant markers significantly increased by 8.4% for SOD and 9.9% for GSH-Px between the preintervention and postintervention measurements, whereas MDA were significantly decreased by 8.7%. In addition, the SOD, GSH-Px, and MDA levels in the GoChi group were significantly different from those in the placebo group at the postintervention time point, with increases of 8.1% and 9.0% and a decrease of 6.0%, respectively. No significant differences were detected between the preintervention and postintervention time points in the placebo group. These results indicate that GoChi increased antioxidant efficacies in humans by stimulating endogenous factors and suggest that continued use beyond 30 days might help prevent or reduce free radical-related conditions.

The effect of active hexose correlated compound in modulating cytosine arabinoside-induced hair loss, and 6-mercaptopurine- and methotrexate-induced liver injury in rodents.

BACKGROUND: Active hexose correlated compound (AHCC) (a mixture of polysaccharides, amino acids, lipids and minerals derived from cultured mycelia of a Basidiomycete mushroom, Lentinula edodes) was used to assess amelioration of alopecia (hair loss) caused by cytosine arabinoside (Ara-C) and modulation of liver injury caused by single doses 6-mercaptopurine (6-MP) plus methotrexate (MTX). METHODS: Follicular integrity and hair growth was assessed in male and female SD neonatal rats (8 days old) treated with a single dose of Ara-C (30 mg/kg/day, i.p.) and AHCC (500 mg/kg/day, p.o.) for 7 consecutive days. The side effects of a single oral dose of 6-MP (2.5mg/kg body weight) plus MTX (30 mg/kg body weight) and their amelioration by treatment with AHCC (1000 mg/kg body weight) for 28 days were assessed in male ddY mice (8 weeks old). RESULTS: Of the Ara-C treated rats 71.4% showed severe alopecia and 28.6% showed moderate alopecia. However, the AHCC (p.o.)-treated Ara-C group was significantly protected from alopecia. Ara-C treated rats had profound loss of hair follicles but the Ara-C plus AHCC-treated group had mild losses of follicles. AHCC supplementation to the 6-MP- and MTX-treated mice significantly increased body weight, erythrocytes, leukocytes and serum albumin, improved liver hypertrophy and degeneration, normalized the activities of serum glutamic oxaloacetic transaminase (sGOT) and serum glutamic pyruvic transaminase (sGPT), and enhanced liver drug-metabolizing enzymes. CONCLUSION: Co-administration of AHCC significantly reduced the side effects associated with Ara-C, 6-MP and MTX. However, the molecular mechanism for AHCC activity and its clinical integrity for use needs defining.

Inhibitory effects of oligonol on phorbol ester-induced tumor promotion and COX-2 expression in mouse skin: NF-kappaB and C/EBP as potential targets.

Plant polyphenols possess anti-oxidant and anti-inflammatory activities and are hence potential candidates for preventing cancer. The present study was aimed at evaluating the anti-inflammatory and anti-tumor promoting activity of oligonol, a formulation of catechin-type oligomers, in mouse skin stimulated with a proto-type tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA). Pretreatment of mouse skin with oligonol significantly inhibited TPA-induced expression of cyclooxygenase-2 (COX-2). Oligonol diminished nuclear translocation and DNA binding of nuclear factor-kappaB (NF-kappaB) via blockade of phosphorylation and subsequent degradation of IkappaB alpha in TPA-treated mouse skin. Moreover, oligonol suppressed TPA-induced DNA binding of CCAAT/enhancer-binding protein (C/EBP) in mouse skin. Oligonol pretreatment also attenuated the phosphorylation and/or catalytic activities of extracellular signal-regulated protein kinase-1/2 (ERK1/2) and p38 mitogen-activated protein (MAP) kinase. Moreover, p38 MAP kinase inhibitor SB203580, but not the MEK inhibitor U0126, negated TPA-induced DNA binding of C/EBP. In addition, oligonol reduced the incidence and the multiplicity of papillomas and squamous cell carcinomas in 7,12-dimethylbenz[a]anthracene (DMBA)-initiated and TPA-promoted mouse skin, and prolonged the survival of tumor-bearing mice. Pretreatment with oligonol diminished the levels of proliferating cell nuclear antigen and expression of COX-2 in papillomas and carcinomas, respectively, as compared to DMBA plus TPA treatment alone. Taken together, the above findings suggest that oligonol inhibits TPA-induced COX-2 expression by blocking the activation of NF-kappaB and C/EBP via modulation of MAP kinases and suppresses chemically induced mouse skin tumorigenesis.

Active hexose correlated compound activates immune function to decrease bacterial load in a murine model of intramuscular infection.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: AHCC appears to induce an early activation of the immune response, leading to an effective clearance of bacteria and rapid recovery.