Ginseng berry polysaccharides on inflammation-associated colon cancer: inhibiting T-cell differentiation, promoting apoptosis, and enhancing the effects of 5-fluorouracil.

BACKGROUND: Ginseng is a commonly used herbal medicine in treating various medical conditions. Chronic gut inflammation is a recognized factor for the development of colorectal cancer (CRC). In this project, Asian ginseng berry polysaccharide preparations were used to assess their effects on CRC and related immune regulation mechanisms. METHODS: Ginseng berry polysaccharide extract (GBPE) and purified ginseng berry polysaccharide portion (GBPP) were used to evaluate their activities on human HCT-116 and HT-29 CRC cell proliferation. Interleukin-8 secretion analysis was performed on HT-29 cells. Naive CD4 cell isolation and T-helper cell differentiation were performed and determined using flow cytometry for Th1 and Treg in addition to cell cycle and apoptotic investigation. RESULTS: GBPE and GBPP significantly inhibited interleukin-8 secretion and cancer cell proliferation, inhibited CD4+IFN-γ+ cell (Th1) differentiation, and decreased CD4+FoxP3+ cell (Treg) differentiation. Compared to the GBPE, GBPP showed more potent antiinflammatory activities on the malignant cells. This is consistent with the observation that GBPP can also inhibit Th1-cell differentiation better, suggesting that it has an important role in antiinflammation, whereas Treg cells hinder the body's immune response against malignancies. Supported by cell cycle and apoptosis data, GBPE and GBPP, at various degrees, remarkably enhanced the anticancer activities of 5-fluorouracil. CONCLUSION: Data from this project suggested that Asian ginseng berry potentially has clinical utility in managing enteric inflammation and suppressing CRC through immunomodulation mechanisms.

Sasa Quelpaertensis Nakai Induced Antidepressant-Like Effect in Ovariectomized Rats.

BACKGROUND: Sasa quelpaertensis Nakai extract (SQE) or dwarf bamboo has been extensively investigated for its antioxidant and anti-inflammatory effects; however, no previous study assessed its effect as an antidepressant agent. Therefore, this study was designed to examine the effect of oral SQE administration in ameliorating menopausal depressive symptoms and to evaluate its mechanisms in ovariectomized rats with repeated stress. METHODS: All experimental groups except normal group underwent ovariectomy and then immobilization for 14 consecutive days. During these 2 weeks, two rat groups received SQE (100 and 300 mg/kg orally) and their cutaneous body temperature was measured. The tail suspension test (TST) and forced swim test (FST) were performed in order to evaluate depression-like behavior. Additionally, enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry were carried out to evaluate the central monoaminergic neurotransmitter levels and activity. RESULTS: Oral SQE (100 mg/kg) administration had reduced immobility time in TST and FST. Additionally, the SQE 100 and 300 mg/kg administration had decreased the cutaneous body temperature in the rats compared to those without treatment. In ELISA analysis, the SQE 100 group expressed elevated levels of serotonin and dopamine in the hypothalamus, prefrontal cortex, and hippocampus. Antityrosine hydroxylase (anti-TH) antibodies showed a tremendous increase in the density of TH positive cells in the locus coeruleus (LC) region of the SQE 100 group. Likewise, the SQE 100 elevated the number of tryptophan hydroxylase (TPH) and protein kinase C (PKC) immunoreactive cell counts and density in the hypothalamic region. CONCLUSION: These results suggested that the oral SQE administration induced the antidepressant-like effect in the ovariectomized rats with repeated stress via upregulating the levels of serotonin and dopamine through enhancing the expression of TH, TPH, and PKC in many brain areas.

Gallocatechin Gallate-Containing Fermented Green Tea Extract Ameliorates Obesity and Hypertriglyceridemia Through the Modulation of Lipid Metabolism in Adipocytes and Myocytes.

Green tea is reported to exert beneficial effects on metabolic disorders through the regulation of lipid metabolism. On the contrary, fermented food products have been introduced to improve human health by modulating immune response and energy metabolism. To maximize health benefit, we applied fermentation processing to green tea. Fermented green tea extract (FGT) inhibited adipogenesis and lipogenesis in cultured adipocytes, whereas it augmented mRNA expression of fatty acid oxidation-related genes in differentiated myocytes. In diet-induced obese mice, FGT blunted body weight and fat mass gain by 69.7% and 56.7%, respectively. FGT also improved circulating triglyceride concentrations by 32.6%. Similar to in vitro results, FGT suppressed lipogenesis and promoted lipid catabolism in peripheral tissues. In addition, FGT administration modulated the composition of certain gut microbiota which are associated with obesity and related metabolic disorders. Among the various components of FGT, gallocatechin gallate is suggested to mediate the effect of FGT on lipid metabolism. Taken together, we propose FGT as a novel functional food to benefit human health by controlling adiposity and lipid metabolism.

Immunostimulating and Antimetastatic Effects of Polysaccharides Purified from Ginseng Berry.

Ginseng root has been used in traditional oriental medicine for the enhancement of immune system function. The immunostimulatory effects of ginseng berry polysaccharides, however, remain unclear. Effects of polysaccharides from ginseng berry on the activation of natural killer (NK) cells and inhibition of tumors are reported. A crude polysaccharide was isolated from ginseng berry as a ginseng berry polysaccharide portion (GBPP) and was further fractionated using gel filtration chromatography to obtain the three polysaccharide fractions GBPP-I, -II and -III. GBPP-I consisted of mainly galactose (46.9%) and arabinose (27.5%). GBPP-I showed a high dose-dependent anticomplementary activity. Stimulation of murine peritoneal macrophages by GBPP-I showed the greatest enhancement of interleukin (IL)-6 and IL-12 and tumor necrosis factor (TNF)- α production. In addition, an ex vivo assay of natural killer (NK) cell activity showed that oral ( p.o.) administration of GBPP-I significantly increased NK cell cytotoxicity in YAC-1 tumor cells and production of granzyme B. Prophylactic intravenous ( i.v.) and p.o. administration of GBPP-I significantly and dose-dependently inhibited lung metastatic activity in B16BL6 melanoma cells. Depletion of NK cells after injection of rabbit anti-asialo GM1 partially abolished the inhibitory effect of GBPP-I on lung metastasis, indicating that NK cells play an important role in anticancer effects. GBPP-I exerts a strong immune-enhancing activity and can prevent cancer metastasis through activation of NK cells and other immune-related cells.

Multiple Effects of Ginseng Berry Polysaccharides: Plasma Cholesterol Level Reduction and Enteric Neoplasm Prevention.

The root of Asian ginseng (Panax ginseng C.A. Meyer) has been used for centuries in Oriental medicine to improve general well-being and to relieve various medical conditions. It is commonly understood that ginsenosides are responsible for the pharmacological activities of ginseng. Compared to the root of ginseng, studies on the berry are considerably limited. In this study, we evaluated the effects of polysaccharides from Asian ginseng berries on plasma lipid levels, chemically-induced enteric inflammation and neoplasm, and cancer chemoprevention in different experimental models. We tested two polysaccharide preparations: regular ginseng berry polysaccharide extract (GBPE) and ginseng berry polysaccharide portion (GBPP, removed MV [Formula: see text]). We first observed that both oral GBPE and oral GBPP significantly reduced plasma cholesterol and triglycerides levels in a dose-related manner in ob/ob mice, without obvious body weight changes. Then, in AOM/DSS-induced acute colitis mice, GBPE and GBPP significantly ameliorated the increased gut disease activity index and inhibited the reduction of the colon length. Further, the berry polysaccharides significantly suppressed chemically-induced pro-inflammatory cytokine levels. This is consistent with the observation that GBPE and GBPP attenuated tumorigenesis in mice by significantly and dose-dependently reducing tumor load. Finally, in vitro HCT-116 and HT-29 human colon cancer cells were used. While these berry preparations had better antiproliferation effects on the HCT-116 than the HT-29 cells, the GBPE had significantly stronger inhibitory effects than GBPP. The observed in vitro GBPE's effect could contribute to the actions of its small-molecule non-polysaccharide compounds due to their direct antiproliferative activities. Results obtained from the present study suggest that ginseng berry polysaccharides may have a therapeutic role in the management of high lipid levels, enteric inflammation, and colon malignancies.

Fermented green tea extract exhibits hypolipidaemic effects through the inhibition of pancreatic lipase and promotion of energy expenditure.

Hyperlipidaemia is a major cause of atherosclerosis and related CVD and can be prevented with natural substances. Previously, we reported that a novel Bacillus-fermented green tea (FGT) exerts anti-obesity and hypolipidaemic effects. This study further investigated the hypotriglyceridaemic and anti-obesogenic effects of FGT and its underlying mechanisms. FGT effectively inhibited pancreatic lipase activity in vitro (IC50, 0·48 mg/ml) and ameliorated postprandial lipaemia in rats (26 % reduction with 500 mg/kg FGT). In hypertriglyceridaemic hamsters, FGT administration significantly reduced plasma TAG levels. In mice, FGT administration (500 mg/kg) for 2 weeks augmented energy expenditure by 22 % through the induction of plasma serotonin, a neurotransmitter that modulates energy expenditure and mRNA expressions of lipid metabolism genes in peripheral tissues. Analysis of the gut microbiota showed that FGT reduced the proportion of the phylum Firmicutes in hamsters, which could further contribute to its anti-obesity effects. Collectively, these data demonstrate that FGT decreases plasma TAG levels via multiple mechanisms including inhibition of pancreatic lipase, augmentation of energy expenditure, induction of serotonin secretion and alteration of gut microbiota. These results suggest that FGT may be a useful natural agent for preventing hypertriglyceridaemia and obesity.

Fermented green tea extract alleviates obesity and related complications and alters gut microbiota composition in diet-induced obese mice.

Obesity is caused by an imbalance between caloric intake and energy expenditure and accumulation of excess lipids in adipose tissues. Recent studies have demonstrated that green tea and its processed products (e.g., oolong and black tea) are introduced to exert beneficial effects on lipid metabolism. Here, we propose that fermented green tea (FGT) extract, as a novel processed green tea, exhibits antiobesity effects. FGT reduced body weight gain and fat mass without modifying food intake. mRNA expression levels of lipogenic and inflammatory genes were downregulated in white adipose tissue of FGT-administered mice. FGT treatment alleviated glucose intolerance and fatty liver symptoms, common complications of obesity. Notably, FGT restored the changes in gut microbiota composition (e.g., the Firmicutes/Bacteroidetes and Bacteroides/Prevotella ratios), which is reported to be closely related with the development of obesity and insulin resistance, induced by high-fat diets. Collectively, FGT improves obesity and its associated symptoms and modulates composition of gut microbiota; thus, it could be used as a novel dietary component to control obesity and related symptoms.

Effects of collagen tripeptide supplement on skin properties: a prospective, randomized, controlled study.

BACKGROUND: Experimental and clinical trials have indicated that dietary supplements can have beneficial effects on skin health. OBJECTIVE: We investigated to evaluate the effect of daily collagen peptide (CP) supplement on skin properties. METHODS: Thirty-two healthy volunteers were randomized to receive either no supplement (Group A), CP 3 g (Group B), CP 3 g, and vitamin C 500 mg (Group C), or vitamin C 500 mg (Group D) daily for 12 weeks. Skin properties evaluated included hydration, transepidermal water loss (TEWL), and elasticity using a corneometer, tewameter, and cutometer, respectively. RESULTS: Changes from baseline in the corneometer were statistically significant between Groups A and B (p = 0.011) and Groups A and C (p = 0.004). There were statistically significant differences in cutometer from baseline between Groups A and B (p = 0.005) and Groups A and C (p = 0.015). There was no significant difference from baseline in the corneometer and cutometer between Groups B and C. The greatest changes in TEWL from baseline were seen in Group B, and the second greatest changes were seen in Group C. CONCLUSIONS: Daily CP supplementation may improve skin hydration and elasticity, but concomitant intake of low-dose vitamin C did not enhance the effect of CP on skin properties.

Inhibitory effects of black soybean on platelet activation mediated through its active component of adenosine.

Owing to the beneficial health effects on human cardiovascular system, soybeans and soy-related products have been a focus of intensive research. Soy isoflavones are known to be primarily responsible for the soy-related biological effects including anti-platelet activity but its in vivo relevancy has not been fully verified. Here we compared the role of adenosine, an active ingredient abundant in black soybean (BB) extract, in the anti-platelet effects of BB, to that of soy isoflavones. At the concentrations existing in BB, isoflavones such as genistein and daidzein could not attenuate collagen-induced platelet aggregation, however, adenosine significantly inhibited platelet aggregation with an equivalent potency to BB, suggesting that adenosine may be the major bioactive component. Consistently, the anti-aggregatory effects of BB disappeared after treatment of adenosine receptor antagonists. The effects of BB are mediated by adenosine through intracellular cAMP and subsequent attenuation of calcium mobilization. Of note, adenosine and BB significantly reduced platelet fibrinogen binding and platelet adhesion, other critical events for platelet activation, which were not affected by isoflavones. Taken together, we demonstrated that adenosine might be the major active ingredient for BB-induced anti-platelet activity, which will shed new light on the roles of adenosine as a bioactive compound in soybeans and soy-related food.

An ethanol extract of Artemisia iwayomogi activates PPARδ leading to activation of fatty acid oxidation in skeletal muscle.

Although Artemisia iwayomogi (AI) has been shown to improve the lipid metabolism, its mode of action is poorly understood. In this study, a 95% ethanol extract of AI (95EEAI) was identified as a potent ligand of peroxisome proliferator-activated receptorδ (PPARδ) using ligand binding analysis and cell-based reporter assay. In cultured primary human skeletal muscle cells, treatment of 95EEAI increased expression of two important PPARδ-regulated genes, carnitine palmitoyl-transferase-1 (CPT1) and pyruvate dehydrogenase kinase isozyme 4 (PDK4), and several genes acting in lipid efflux and energy expenditure. Furthermore, 95EEAI stimulated fatty acid oxidation in a PPARδ-dependent manner. High-fat diet-induced obese mice model further indicated that administration of 95EEAI attenuated diet-induced obesity through the activation of fatty acid oxidation in skeletal muscle. These results suggest that a 95% ethanol extract of AI may have a role as a new functional food material for the prevention and/or treatment of hyperlipidermia and obesity.

Effect of Aspergillus oryzae-challenged germination on soybean isoflavone content and antioxidant activity.

Application of microbial stress to soybean during germination induces the accumulation of phytoalexins, which have many health benefits. In this study, the effects of stress induced by Aspergillus oryzae on the phytochemical composition of germinating soybeans were investigated, and their radical scavenging activity was compared with those of ungerminated (US) and germinated (GS) soybeans. Additionally, the antioxidant activity of coumestrol, a soybean phytoalexin, against hydrogen peroxide-induced reactive oxygen species (ROS) was investigated in HepG2 cells. A. oryzae exposure significantly decreased the total isoflavone content and induced coumestrol and glyceollin I. A. oryzae-challenged germinated soybeans exhibited the highest radical scavenging activity (IC(50) = 0.55 mg/mL) as compared to US and GS. Coumestrol exhibited significantly higher radical scavenging activity than daidzein and genistein. Furthermore, coumestrol significantly prevented hydrogen peroxide-induced ROS production and lipid peroxidation and inhibited decreases in cell viability, intracellular glutathione (GSH) levels, and superoxide dismutase (SOD) activity. These results indicate that using food-grade A. oryzae to elicit the biosynthesis of phytoalexins alters the secondary metabolite profiles of the soybeans and offers enhanced bioactivity of soybean as a functional food ingredient.

Black soybean extract can attenuate thrombosis through inhibition of collagen-induced platelet activation.

Many clinical trials have demonstrated the beneficial effects of soybean (Glycine max) on general cardiovascular health. Among a variety of soybeans, black soybean is known to display diverse biological activities superior to those of yellow and green soybeans, such as in antioxidant, anti-inflammatory and anticancer activities. However, few studies have been directed on the effect of black soybean on cardiovascular function. In this study, we aimed to investigate the effect of black soybean extract (BB) on platelet activation, a key contributor to thrombotic diseases. In freshly isolated human platelets, BB has shown potent inhibitory activity on collagen-induced platelet aggregation, while yellow soybean extract had marginal activity only. BB also attenuated serotonin secretion and P-selectin expression, which are important factors for the platelet-tissue interaction along with thromboxane A(2) formation. These in vitro results were further confirmed in an ex vivo platelet aggregation measurement and in vivo venous thrombosis model where oral administration of BB reduced collagen-induced platelet aggregation and FeCl(3)-induced thrombus formation significantly. A potential active ingredient for antiplatelet effects of BB was isolated and identified to be adenosine through bioassay-directed fractionation and NMR and ESI-MS analyses. These results indicate that black soybean can be a novel dietary supplement for the prevention of cardiovascular risks and the improvement of blood circulation.

Effects of chitooligosaccharide lactate salt on activity of acetaldehyde dehydrogenase.

Chitooligosaccharides (COS), a kind of oligosaccharide made from chitin or chitosan, have been used a popular remedy for hangovers. In this study we investigated the in vitro effect of COS lactate salt on ethanol-induced cytotoxicity and the in vivo effect of short-term COS lactate salt feeding on ethanol-induced hangover. Pretreatment of HepG2 cells with COS lactate salt significantly reduced ethanol-induced cytotoxicity and suppressed generation of reactive oxygen species. In addition, COS lactate salt dose-dependently increased acetaldehyde dehydrogenase (ALDH) activity in vitro and reversed the ALDH inhibition induced by daidzin. Furthermore, oral administration of COS lactate salt (200 mg/kg) for 5 days significantly decreased the blood levels of alcohol and acetaldehyde in ethanol-treated mice. It was also demonstrated that hepatic mitochondrial ALDH activity was significantly increased in COS lactate salt-treated mice. Taken together, these findings indicate that COS lactate salt may have efficacy for the management of alcoholic hangovers.