The Tumor Growth Inhibitory Effect of a Standardized Extract of Cultured Lentinula edodes Mycelia Using Patient Derived Xenograft Model.

Patient derived xenograft (PDX) is a powerful tool to confirm pharmacological efficacy in non-clinical studies for the development of various drugs including anti-cancer agents and therapeutic research. A standardized extract of cultured Lentinula edodes mycelia, a product name AHCC® is produced by Amino Up Co., Ltd. (Sapporo, Japan). In this study, we investigated the inhibitory effect of AHCC® on the growth of tumor PDX in Super SCID (severe combined immunodeficiency) mice. Effects of AHCC® and BCG administration on the growth of renal cancer PDX implanted in Super SCID mice were evaluated by PDX growth curve. Tendency for the effects on the growth of renal cancer PDX in Super SCID by administration of AHCC® and BCG before implanting the PDX were demonstrated. The effects of the oral administration of AHCC® on the growth of renal, invasive and non-invasive breast cancer PDX in Super SCID mice were studied. In Super SCID mice transplanted with renal cancer PDX, AHCC® significantly suppressed tumor proliferation from the day 48 to 83 after transplantation. In two types of breast cancer PDX, tendency of the growth inhibitory effects of AHCC® were shown by PDX growth curve. Significant inhibitory effect was found at only one time point for during proliferation in each PDX. Super SCID-PDX model has the potential to be a useful tool to investigate for the effect of functional foods.

Synergistic effect of standardized extract of Asparagus officinalis stem and heat shock on progesterone synthesis with lipid droplets and mitochondrial function in bovine granulosa cells.

Progesterone (P4) is a well-known steroid hormone that plays a key role in oocyte growth and the maintenance of pregnancy in mammals, including cattle. Heat stress (HS) has an adverse effect on P4 synthesis through an imbalance in the cellular redox status. We have recently revealed that a standardized extract of Asparagus officinalis stem (EAS) increases P4 through non-HS induction of heat shock protein 70 (HSP70) and a synergistic increase of HSP70 by enhancing the intracellular redox balance, which was adversely affected by HS in bovine granulosa cells (GCs). Bovine GCs collected from bovine ovarian follicles were cultured at 38.5 °C and 41 °C for 12 h with or without 5 mg/mL EAS. After treatment, cells and culture suppernatant were collected for the analysis. Enzyme-linked immunosorbent assay (ELISA) was performed to detect in P4 levels. Quantitative reverse-transcription polymerase chain reaction (RT-qPCR) was used to detect expression of steroidogenesis related genes. Fluorescence staining was used to detect mitochondrial activity and lipid droplet. P4 level was increased by EAS treatment in association with increase in steroidogenic acute regulatory protein (STAR), 3ß-hydroxysteroid dehydrogenase (3ß-HSD), mitochondrial membrane activity and lipid droplet both under non-HS and HS conditions. Notably, synergistic effect of EAS with HS co-treatment was observed to show a greater increase in P4 synthesis when comparison with EAS treatment under non-HS condition. Furthermore, inhibition of HSP70 significantly reduced EAS-induced P4 synthesis, mitochondrial activity and synthesis of lipid droplets. These results suggest that P4 synthesis by EAS is mediated by the steroidogenesis pathway via HSP70-regulated activation of STAR and 3ß-HSD, together with improved mitochondrial activity and lipid metabolism in bovine GCs. Moreover, effect of EAS has a synergistic effect of with HSP70-regulated steroidogenesis pathway.

AHCC®, a Standardized Extract of Cultured Lentinula Edodes Mycelia, Promotes the Anti-Tumor Effect of Dual Immune Checkpoint Blockade Effect in Murine Colon Cancer.

Treatment strategies combining immune checkpoint blockade (ICB) with other agents have emerged as a promising approach in the treatment of cancers. AHCC®, a standardized extract of cultured Lentinula edodes mycelia, has been reported to inhibit tumor growth and enhance immune cell function. Here we investigated whether AHCC® promotes the therapeutic effect of immunotherapy in cancers. A combination of oral AHCC® and dual immune checkpoint blockade (DICB), including PD-1/CTLA-4 blockade, had reduced tumor growth and increased granzyme B and Ki-67 expression by tumor-infiltrating CD8+ T cells in MC38 colon cancer bearing mice compared to a combination of water and DICB. In the same tumor bearing mice, AHCC® and DICB treatment also altered the composition of the gut microbiome with the increased abundance of the species of Ruminococcaceae family which is associated with increased therapeutic efficacy of immunotherapy. The anti-tumor effect of AHCC® and DICB was not found in MC38 tumor-bearing mice treated with antibiotics. These data suggest that AHCC® increases the anti-tumor effect of DICB by enhancing T cell function and affecting the gut microbiome.

Standardized Extract of Asparagus officinalis Stem Attenuates SARS-CoV-2 Spike Protein-Induced IL-6 and IL-1ß Production by Suppressing p44/42 MAPK and Akt Phosphorylation in Murine Primary Macrophages.

Excessive host inflammation following infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is associated with severity and mortality in coronavirus disease 2019 (COVID-19). We recently reported that the SARS-CoV-2 spike protein S1 subunit (S1) induces pro-inflammatory responses by activating toll-like receptor 4 (TLR4) signaling in macrophages. A standardized extract of Asparagus officinalis stem (EAS) is a unique functional food that elicits anti-photoaging effects by suppressing pro-inflammatory signaling in hydrogen peroxide and ultraviolet B-exposed skin fibroblasts. To elucidate its potential in preventing excessive inflammation in COVID-19, we examined the effects of EAS on pro-inflammatory responses in S1-stimulated macrophages. Murine peritoneal exudate macrophages were co-treated with EAS and S1. Concentrations and mRNA levels of pro-inflammatory cytokines were assessed using enzyme-linked immunosorbent assay and reverse transcription and real-time polymerase chain reaction, respectively. Expression and phosphorylation levels of signaling proteins were analyzed using western blotting and fluorescence immunomicroscopy. EAS significantly attenuated S1-induced secretion of interleukin (IL)-6 in a concentration-dependent manner without reducing cell viability. EAS also markedly suppressed the S1-induced transcription of IL-6 and IL-1ß. However, among the TLR4 signaling proteins, EAS did not affect the degradation of inhibitor κBα, nuclear translocation of nuclear factor-κB p65 subunit, and phosphorylation of c-Jun N-terminal kinase p54 subunit after S1 exposure. In contrast, EAS significantly suppressed S1-induced phosphorylation of p44/42 mitogen-activated protein kinase (MAPK) and Akt. Attenuation of S1-induced transcription of IL-6 and IL-1ß by the MAPK kinase inhibitor U0126 was greater than that by the Akt inhibitor perifosine, and the effects were potentiated by simultaneous treatment with both inhibitors. These results suggest that EAS attenuates S1-induced IL-6 and IL-1ß production by suppressing p44/42 MAPK and Akt signaling in macrophages. Therefore, EAS may be beneficial in regulating excessive inflammation in patients with COVID-19.

A standardized extract of Asparagus officinalis stem improves HSP70-mediated redox balance and cell functions in bovine cumulus-granulosa cells.

Heat shock (HS) protein 70 (HSP70), a well-known HS-induced protein, acts as an intracellular chaperone to protect cells against stress conditions. Although HS induces HSP70 expression to confer stress resistance to cells, HS causes cell toxicity by increasing reactive oxygen species (ROS) levels. Recently, a standardized extract of Asparagus officinalis stem (EAS), produced from the byproduct of asparagus, has been shown to induce HSP70 expression without HS and regulate cellular redox balance in pheochromocytoma cells. However, the effects of EAS on reproductive cell function remain unknown. Here, we investigated the effect of EAS on HSP70 induction and oxidative redox balance in cultured bovine cumulus-granulosa (CG) cells. EAS significantly increased HSP70 expression; however, no effect was observed on HSP27 and HSP90 under non-HS conditions. EAS decreased ROS generation and DNA damage and increased glutathione (GSH) synthesis under both non-HS and HS conditions. Moreover, EAS synergistically increased HSP70 and HSF1 expression and increased progesterone levels in CG cells. Treatment with an HSP70 inhibitor significantly decreased GSH level, increased ROS level, and decreased HSF1, Nrf2, and Keap1 expression in the presence of EAS. Furthermore, EAS significantly increased progesterone synthesis. Thus, EAS improves HSP70-mediated redox balance and cell function in bovine CG cells.

ETAS®50 Attenuates Ultraviolet-B-Induced Interleukin-6 Expression by Suppressing Akt Phosphorylation in Normal Human Dermal Fibroblasts.

We recently reported that ETAS 50, a standardized extract from the Asparagus officinalis stem, exerted anti-inflammatory effects on ultraviolet-B- (UV-B-) irradiated normal human dermal fibroblasts (NHDFs) by inhibiting nuclear factor-κB p65 nuclear import and the resulting interleukin-1ß (IL-1ß) expression. To further elucidate the antiphotoaging potency of ETAS 50, we examined the anti-inflammatory effects on UV-B-irradiated NHDFs by focusing on the stress-activated mitogen-activated protein kinase (MAPK) and Akt signaling pathways. NHDFs were treated with 1 mg/mL of ETAS 50 or dextrin (vehicle control) after UV-B irradiation (20 mJ/cm2) for different time periods. Phosphorylation levels of c-Jun N-terminal kinase (JNK), p38 MAPK, and Akt were analyzed by western blotting. IL-6 mRNA levels were analyzed by real-time polymerase chain reaction. UV-B-irradiated NHDFs showed increased phosphorylation levels of JNK, p38 MAPK, and Akt, as well as increased mRNA levels of IL-6. ETAS 50 treatment after UV-B irradiation suppressed the increased phosphorylation levels of Akt without affecting those of JNK and p38 MAPK. ETAS 50 as well as Akt inhibitor Perifosine repressed UV-B irradiation-induced IL-6 mRNA expression. These results suggest that ETAS 50 treatment represses UV-B irradiation-induced IL-6 expression by suppressing Akt phosphorylation. The present findings demonstrate the potential of ETAS 50 to prevent photoaging by attenuating UV-B irradiation-induced proinflammatory responses in skin fibroblasts.

A standardized extract of Asparagus officinalis stem prevents reduction in heat shock protein 70 expression in ultraviolet-B-irradiated normal human dermal fibroblasts: an in vitro study.

BACKGROUND: Heat shock protein 70 (HSP70) exhibits protective effects against ultraviolet (UV)-induced premature skin aging. A standardized extract of Asparagus officinalis stem (EAS) is produced as a novel and unique functional food that induces HSP70 cellular expression. To elucidate the anti-photoaging potencies of EAS, we examined its effects on HSP70 expression levels in UV-B-irradiated normal human dermal fibroblasts (NHDFs). METHODS: NHDFs were treated with 1 mg/mL of EAS or dextrin (vehicle control) prior to UV-B irradiation (20 mJ/cm2). After culturing NHDFs for different time periods, HSP70 mRNA and protein levels were analyzed using real-time polymerase chain reaction and western blotting, respectively. RESULTS: UV-B-irradiated NHDFs showed reduced HSP70 mRNA levels after 1-6 h of culture, which were recovered after 24 h of culture. Treatment with EAS alone for 24 h increased HSP70 mRNA levels in the NHDFs, but the increase was not reflected in its protein levels. On the other hand, pretreatment with EAS abolished the UV-B irradiation-induced reduction in HSP70 expression at both mRNA and protein levels. These results suggest that EAS is capable to preserve HSP70 quantity in UV-B-irradiated NHDFs. CONCLUSIONS: EAS exhibits anti-photoaging potencies by preventing the reduction in HSP70 expression in UV-irradiated dermal fibroblasts.

Anti-Inflammatory Effect of ETAS®50 by Inhibiting Nuclear Factor-κB p65 Nuclear Import in Ultraviolet-B-Irradiated Normal Human Dermal Fibroblasts.

Ultraviolet (UV) irradiation induces proinflammatory responses in skin cells, including dermal fibroblasts, accelerating premature skin aging (photoaging). ETAS 50, a standardized extract from the Asparagus officinalis stem, is a novel and unique functional food that suppresses proinflammatory responses of hydrogen peroxide-stimulated skin fibroblasts and interleukin- (IL-) 1ß-stimulated hepatocytes. To elucidate its antiphotoaging potencies, we examined whether ETAS 50 treatment after UV-B irradiation attenuates proinflammatory responses of normal human dermal fibroblasts (NHDFs). UV-B-irradiated NHDFs showed reduced levels of the cytosolic inhibitor of nuclear factor-κB α (IκBα) protein and increased levels of nuclear p65 protein. The nuclear factor-κB nuclear translocation inhibitor JSH-23 abolished UV-B irradiation-induced IL-1ß mRNA expression, indicating that p65 regulates transcriptional induction. ETAS 50 also markedly suppressed UV-B irradiation-induced increases in IL-1ß mRNA levels. Immunofluorescence analysis revealed that ETAS 50 retained p65 in the cytosol after UV-B irradiation. Western blotting also showed that ETAS 50 suppressed the UV-B irradiation-induced increases in nuclear p65 protein. Moreover, ETAS 50 clearly suppressed UV-B irradiation-induced distribution of importin-α protein levels in the nucleus without recovering cytosolic IκBα protein levels. These results suggest that ETAS 50 exerts anti-inflammatory effects on UV-B-irradiated NHDFs by suppressing the nuclear import machinery of p65. Therefore, ETAS 50 may prevent photoaging by suppressing UV irradiation-induced proinflammatory responses of dermal fibroblasts.

Enzyme-Treated Asparagus Extract (ETAS) Facilitates the Turnover of UV-B-Irradiated Keratinocytes.

Enzyme-treated asparagus extract (ETAS) is prepared from the lower, residual parts of asparagus, and some functionalities, such as anti-oxidative and neuroprotective activities, have been suggested. The purpose of the present study was to investigate the effects of ETAS on photoaging in the epidermal layer of the skin using cultured keratinocytes. Normal human epidermal keratinocytes were irradiated or left unirradiated with UV-B (10 mJ/cm2) and incubated with ETAS (0.5 or 2 mg/mL) or vehicle. After 3 or 13 h, molecular examinations were performed, and after 24 or 48 h, cell viabilities were determined by a CCK-8 assay. ETAS addition may induce keratinocyte migration and proliferation as well as apoptosis under molecular examination. These results suggest that ETAS might accelerate turnover of keratinocytes.

Effects of AHCC® on Immune and Stress Responses in Healthy Individuals.

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.

Active hexose correlated compound modulates LPS-induced hypotension and gut injury in rats.

We hypothesized that AHCC; (Amino UP Chemical Co., Ltd., Sapporo, Japan), a mushroom mycelium extract obtained from liquid culture of Lentinula edodes, restores immune function in LPS-induced inflammation in the gut, especially when the nitric oxide signaling pathway is impaired. This is the first inter-disciplinary proposal to identify molecular mechanisms involved in LPS-induced immune dysfunction in the gut in conscious animals treated or non-treated with AHCC, a promoter of immune support. Specifically, we have tested the effects of AHCC on LPS-induced deleterious effects on blood pressure and gut injury in conscious rats. The time course of biological markers of innate/acquired immune responses, and inflammation/oxidative stress is fully described in the present manuscript. Rats were randomly assigned into 3 groups (N=6 per group). Group 1 received 10% of AHCC in drinking water for 5days; Group 2 received lipopolysaccharide (LPS; Escherichia coli 0111:B4 purchased from Sigma) only at 20mg/kg IV; Group 3 received combined treatments (AHCC + LPS). LPS was administered at 20mg/kg IV, 5days following AHCC treatment. We have demonstrated that AHCC decreased the LPS-deleterious effects of blood pressure and also decreased inflammatory markers e.g., cytokines, nitric oxide and edema formation. Finally, AHCC diminished lymphocyte infiltration, restoring gut architecture. Because AHCC was administered prior to LPS, our results indicate the potential impact of AHCC's prophylactic effects on LPS inflammation. Consequently, additional experiments are warrant to assess its therapeutic effects in sepsis-induced inflammation.

Effect of Enzyme-Treated Asparagus Extract (ETAS) on Psychological Stress in Healthy Individuals.

The aim of this study was to examine the effectiveness of Enzyme-Treated Asparagus Extract (ETAS) on improving stress response. A randomized, double-blind, placebo-controlled cross-over trial was undertaken in healthy volunteers. ETAS (150 mg/d) or a placebo was consumed for 28 d, with a washout period. Psychological parameters were examined using a self-report scale questionnaire and psychological stress was applied using the Uchida-Kraepelin (U-K) test. During the stress load, autonomic nervous function was analyzed. After the stress load, a profile of mood states (POMS) psychological rating was performed, and serum cortisol, plasma catecholamine, salivary secretory immunoglobulin A (sIgA), and salivary cortisol were analyzed. ETAS intake improved the self-reported rating for the items "Feel tired," "Hard to get up," and "Feel heavy" in the psychological questionnaire; ameliorated the self-reported rating for the items "Depression-Dejection" and "Fatigue" in the POMS questionnaire; and increased salivary sIgA levels after the U-K test. In contrast, serum and salivary cortisol levels, and plasma catecholamine did not change. During the U-K test, ETAS significantly upregulated the sympathetic nerve activity. Furthermore, ETAS intake significantly increased the number of answers and the number of correct answers in the U-K test, suggesting that it might improve office work performance with swiftness and accuracy under stressful conditions. In conclusion, ETAS supplementation reduced feelings of dysphoria and fatigue, ameliorated quality of sleep, and enhanced stress-load performance as well as promoted stress response by increasing salivary sIgA levels. These data suggest ETAS intake may exert beneficial effects, resulting from well-controlled stress management, in healthy individuals.

Global Liver Gene Expression Analysis on a Murine Metabolic Syndrome Model Treated by Low-molecular-weight Lychee Fruit Polyphenol (Oligonol®).

BACKGROUND/AIM: Oligonol® (OLG) is a low-molecular-weight lychee fruit polyphenol mainly containing catechin-type monomers and oligomers of proanthocyanidins. Dietary OLG supplementation reportedly improves lipid metabolism disorder and lowers the visceral fat level in animal and human studies. Thus, we investigated the mechanism behind the protective and beneficial effects of OLG on a Western diet (WD)-induced metabolic syndrome (MetS) of a murine model. MATERIALS AND METHODS: Using the C57BL/6J mouse for the MetS model, mice were divided into three groups: control (normal diet: ND), Western diet (WD) and WD + 0.5% OLG (OLG) groups. The WD group was fed a high-calorie (high fructose plus high fat) diet for 12 weeks to develop MetS. At week 12, all mice were sacrificed and the blood and liver were obtained for histological and biological examinations and RNA sequencing (RNA-Seq). RESULTS: Body weight, liver weight, plasma triglycerides (TG), total cholesterol (T-Cho) and alanine aminotransferase (ATS) levels of both OLG groups were significantly lower than those of the WD group. On histological examination of the liver, the area of fatty deposits was shown to be suppressed by OLG administration. Expression gene analysis in the liver of WD- versus OLG-fed mice by RNA-Seq showed that 464/45,706 genes exhibited a significant change of expression (corrected p-value <0.05, absolute value of fold change (FC) ≥2). Gene network analysis showed that genes related to hepatic steatosis, liver inflammation and tumor invasion were inactivated in the OLG group. In particular, the lipid metabolism-related genes Lpin1, Adig and Cidea were regulated by OLG administration. CONCLUSION: OLG may function to suppress MetS and the progression of geriatric diseases in WD-fed mice by regulating the expression of lipid metabolism, inflammation and tumor-related genes in the liver.

Enzyme-Treated Asparagus Extract Attenuates Hydrogen Peroxide-Induced Matrix Metalloproteinase-9 Expression in Murine Skin Fibroblast L929 Cells.

Enzyme-treated asparagus extract (ETAS) exerts a wide variety of beneficial biological actions including facilitating anti-cortisol stress and neurological anti-aging responses. However, the anti-skin aging effects of ETAS remain to be elucidated. Reactive oxygen species (ROS) play pivotal roles in skin aging. Increased ROS levels in fibroblasts in response to ultraviolet irradiation activate c-Jun N-terminal kinase (JNK) and its downstream transcription factor activator protein-1 (AP-1), and the resultant gene expression of matrix metalloproteinase (MMP) isoforms accelerates collagen breakdown in the dermis. Therefore, we explored whether ETAS has anti-skin aging effects by attenuating the oxidative stress responses in fibroblasts. Simultaneous treatment of murine skin L929 fibroblasts with hydrogen peroxide (H2O2) and either ETAS or dextrin showed that ETAS significantly suppressed H2O2-induced expression of MMP-9 mRNA as measured by real-time polymerase chain reaction. ETAS also clearly suppressed H2O2-stimulated phosphorylation of c-Jun (AP-1 subunit) and JNK as determined by Western blot. However, ETAS did not affect the increased amounts of carbonyl proteins in response to H2O2, also as determined by Western blotting. These results suggest that ETAS diminishes cellular responsiveness to ROS but does not scavenge ROS. Thus, ETAS has the potential to prevent skin aging through attenuating the oxidative stress responses in dermal fibroblasts.

Perilla leaf extract prevents atopic dermatitis induced by an extract of Dermatophagoides farinae in NC/Nga mice.

BACKGROUND: Perilla (Perilla frutescens Britton) leaf comprises many types of active components, mainly flavonoids, and acts as an anti-inflammatory agent in in vitro and in vivo atopic dermatitis (AD) models. OBJECTIVE: We investigated the effects of orally administered perilla leaf extract (PLE) on the symptoms of AD induced by Dermatophagoides farinae extract (DFE) in NC/Nga AD model mice. METHODS: The mice were allowed free intake of 0.5% PLE. Skin lesions were assessed, and blood was sampled from the caudal vein on days 0, 7, 14, 21, and 31. On day 31, all mice were sacrificed to obtain blood, skin, spleen, and intestinal tissue samples. RESULTS: The assessment scores of the skin lesions and total serum IgE levels of PLE-treated mice (PLE group) were significantly lower than DFE-treated mice (DFE group) on days 7, 14, and 21. On day 31, the serum periostin and thymus and activation-regulated chemokine (TARC) levels in the PLE group were significantly lower than those in the DFE group. Histological analysis of the skin revealed that hyperplasia of the epidermal and dermal layers and infiltration of inflammatory cells (cell infiltration in corium tissues) were suppressed by PLE. Periostin deposition was observed in the skin tissue obtained from the DFE group. Moreover, the CD4+/CD8+ ratio of splenic T cells was suppressed in the PLE group but not in the DFE group.

Enzyme-Treated Asparagus Extract Prevents'Hydrogen Peroxide-Induced Pro-Inflammatory Responses by Suppressing p65 Nuclear Translocation in Skin L929 Fibroblasts.

We recently reported that enzyme-treated asparagus extract (ETAS) attenuates hydrogen peroxide (H(2)0(2))-stimulated matrix metalloproteinase-9 expression in skin fibroblast L929 cells. To further elucidate the anti-aging effects of ETAS on skin, we examined whether ETAS has preventive effects on H202-induced pro-inflammatory responses of skin fibroblasts. H(2)0(2) induced Ser536 phosphorylation and nuclear accumulation of nuclear factor-κB (NF-κB) p65, and increased the mRNA levels .of interleukin-12α (IL-12α)-and inducible nitric oxide synthase (iNOS) in L929 cells. Pretreatment of the cells with JSH-23, an inhibitor of NF-κB nuclear translocation, abolished the H(2)(0(2)-induced expression of IL-12α and iNOS, indicating that the increased transcription is regulated by p65. The H(2)0(2)-stimulated nuclear accumulation of p65 and-induction of IL12a and iNOS mRNA were significantly attenuated after pretreatment with ETAS for 3 h, and these responses were completely abolished when the duration was extended to 24 h. However, ETAS did not affect the H(2)0(2)-stimulated degradation of IκBα and phosphorylation of p65. On the other hand, ETAS treatment for 24 h resulted in decreased protein levels of importin-α. These results suggest that ETAS prevents pro-inflammatory responses by suppressing the p65 nuclear translocation in skin fibroblasts induced by H202.

Effects of active hexose correlated compound on the seasonal variations of immune competence in healthy subjects.

The aim of this study was to evaluate the effects of active hexose correlated compound intake on the immune competence in healthy volunteers. Thirty-four subjects were randomized to receive placebo or active hexose correlated compound at 1.0 g/d for 4 weeks in early winter. Natural killer cell activity was significantly increased in both groups during the study period, the natural killer cell number, however, was not altered in the active hexose correlated compound group while placebo group showed remarkable decline. In addition, the score of immunological vigor, an index of total immune competence, was maintained in the active hexose correlated compound group although that of placebo group lowered during the test period. These results suggested that the continuous active hexose correlated compound intake maintained the immune competence against the seasonal change.

Effects of enzyme-treated asparagus extract on heat shock protein 70, stress indices, and sleep in healthy adult men.

Enzyme-treated asparagus extract (ETAS) has been developed as a novel anti-stress functional food ingredient that is produced from asparagus. Two human intervention trials with ETAS were conducted in healthy adult male volunteers. Study 1 was a randomized, double-blind, placebo-controlled study to assess the effects of ETAS on expression of heat shock protein 70 (HSP70) mRNA in blood and the autonomic nervous system (ANS). The ETAS group showed a tendency to enhance HSP70 mRNA expression level compared to the placebo group. Several ANS condition parameters were significantly improved in the ETAS group when compared to the placebo group. In Study 2, a randomized, double-blind, placebo-controlled, crossover trial investigated the influence on stress-related hormones and sleep. Serum and salivary cortisol levels were significantly elevated compared to baseline during the placebo period, but remained unchanged during the ETAS period. The salivary chromogranin A level was significantly decreased in the ETAS-treated subjects compared to their baseline levels. The actual sleep time was not significantly different between ETAS and placebo. However, when the subjects were divided into two categories based on sleep efficiency or the average of night sleeping time, ETAS intake was effective to modulate the sleep state among those with low sleep efficiency or excess sleep time.

Isolation, structural elucidation, and biological evaluation of a 5-hydroxymethyl-2-furfural derivative, asfural, from enzyme-treated asparagus extract.

A novel 5-hydroxymethyl-2-furfural (HMF; 1) derivative, which is named asfural (compound 2), was isolated from enzyme-treated asparagus extract (ETAS) along with HMF (1) as a heat shock protein 70 (HSP70) inducible compound. The structure of compound 2 was elucidated on the basis of its spectroscopic data from HREIMS and NMR, whereas the absolute configuration was determined using chiral HPLC analysis, compared to two synthesized compounds, (S)- and (R)-asfural. As a result, compound 2 derived from ETAS was assigned as (S)-(2-formylfuran-5-yl)methyl 5-oxopyrrolidine-2-carboxylate. When compound 2, synthesized (S)- and (R)-asfural, and HMF (1) were evaluated in terms of HSP70 mRNA expression-enhancing activity in HL-60 cells, compound 2 and (S)-asfural significantly increased the expression level in a concentration-dependent manner. HMF (1) also showed significant activity at 0.25 mg/mL.