Two Prenylated Chalcones, 4-Hydroxyderricin, and Xanthoangelol Prevent Postprandial Hyperglycemia by Promoting GLUT4 Translocation via the LKB1/AMPK Signaling Pathway in Skeletal Muscle Cells.

SCOPE: Stimulation of glucose uptake in the skeletal muscle is crucial for the prevention of postprandial hyperglycemia. Insulin and certain polyphenols enhance glucose uptake through the translocation of glucose transporter 4 (GLUT4) in the skeletal muscle. The previous study reports that prenylated chalcones, 4-hydroxyderricin (4-HD), and xanthoangelol (XAG) promote glucose uptake and GLUT4 translocation in L6 myotubes, but their underlying molecular mechanism remains unclear. This study investigates the mechanism in L6 myotubes and confirms antihyperglycemia by 4-HD and XAG. METHODS AND RESULTS: In L6 myotubes, 4-HD and XAG promote glucose uptake and GLUT4 translocation through the activation of adenosine monophosphate-activated protein kinase (AMPK) and liver kinase B1 (LKB1) signaling pathway without activating phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) and Janus kinases (JAKs)/signal transducers and activators of transcriptions (STATs) pathways. Moreover, Compound C, an AMPK-specific inhibitor, as well as siRNA targeting AMPK and LKB1 completely canceled 4-HD and XAG-increased glucose uptake. Consistently, oral administration of 4-HD and XAG to male ICR mice suppresses acute hyperglycemia in an oral glucose tolerance test. CONCLUSION: In conclusion, LKB1/AMPK pathway and subsequent GLUT4 translocation in skeletal muscle cells are involved in Ashitaba chalcone-suppressed acute hyperglycemia.

Black Soybean Seed Coat Extract Improves Endothelial Function and Upregulates Oxidative Stress Marker Expression in Healthy Volunteers by Stimulating Nitric Oxide Production in Endothelial Cells.

Black soybean seed coat extract (BE) contains multiple bioactive polyphenols, including flavan-3-ols and anthocyanins. BE improves endothelial function; however, it is unclear whether BE protects endothelial cells from senescence. In this study, we examined the effects of BE on endothelial cell senescence and vascular function in healthy individuals. High concentrations of glucose were used to induce senescence in bovine aortic endothelial cells incubated with BE. Senescence, vascular function, and oxidative stress markers were measured. Incubation with BE remarkably inhibited senescence-associated ß-galactosidase and lactate dehydrogenase activities and dose dependently reduced intracellular reactive oxygen species levels in bovine aortic endothelial cells. BE treatment increased the levels of endothelial nitric oxide synthase (eNOS) mRNA and endothelial nitric oxide (NO) metabolites and increased the mRNA expression of klotho, a gene associated with an antiaging phenotype. To examine the effects of BE in humans, we conducted a clinical study using the second derivative of the fingertip photoplethysmogram to investigate vascular function and aging in 24 healthy volunteers. The participants consumed BE supplements (100 mg/day) or a placebo for 2 weeks. When compared with the placebo group, the BE group showed considerably improved vascular function, NO metabolite levels, and oxidative stress. These results suggest that BE supplementation improves endothelial function, possibly through antioxidant activity and NO production, and may consequently reduce the cardiovascular risk associated with aging. BE supplementation may be an effective and safe approach to reduce the risk of atherosclerosis and cardiovascular disease; however, additional studies investigating chronic vascular inflammation are needed.

Single oral administration of quercetin glycosides prevented acute hyperglycemia by promoting GLUT4 translocation in skeletal muscles through the activation of AMPK in mice.

Quercetin is a natural flavonol and has various health beneficial functions. Our pervious study demonstrated that long-term feeding (13 weeks) of quercetin and its glycosides, isoquercitrin, rutin, and enzymatically modified isoquercitrin, which is a mixture of quercetin monoglycoside and its oligoglycosides, prevented hyperglycemia and adiposity in mice fed a high-fat diet but not standard diet. It is, however, unclear whether a single administration of these compounds prevent postprandial hyperglycemia or not. In the present study, we estimated their prevention effect on acute hyperglycemia by an oral glucose tolerance test in ICR mice and investigated its mechanism. It was found that quercetin glycosides, but not the aglycone, suppressed acute hyperglycemia and isoquercitrin showed the strongest effect among the glycosides. As the underlying mechanism, quercetin glycosides promoted translocation of glucose transporter 4 to the plasma membrane of skeletal muscle of mice through phosphorylation of adenosine monophosphate-activated protein kinase and its upstream Ca2+/calmodulin-dependent protein kinase kinase ß without activating the insulin- and JAK/STAT-signal pathways. In conclusion, single oral administration of quercetin glycosides prevented a blood sugar spike by promoting glucose transporter 4 translocation through activating the CAMKKß/AMPK signaling pathway.

Black soybean seed coat polyphenols have different effects on glucose and lipid metabolism in growing and young adult mice.

Black soybean contains flavan-3-ols and cyanidin 3-O-glucoside in its seed coat. Polyphenol-rich black soybean seed coat extract (BE) possesses various health benefits, such as antioxidant, anti-obesity, and anti-hyperglycemic effects. However, these functions have been evaluated mainly in the growing stage of animals, and there is no comparison data for different life stages. In this present study, we compared the effect of BE in growing (5-week old) and young adult (22-week old) ICR male mice. These mice were given an AIN 93M diet containing 2.0% BE for 4 weeks. BE did not affect body weight gain in both growing and young adult mice, but it suppressed mesenteric and subcutaneous white adipose tissue weights and decreased the cell size. BE also significantly suppressed plasma free-fatty acid levels. The effect of both BE and life stages were observed in the protein expression of adipogenesis-related transcription factors; in particular, BE suppressed the expression of C/EBPα and PPARγ. No significant change was observed in lipolysis and lipogenesis factors in the white adipose tissue and liver. Alternatively, BE showed low glucose tolerance without affecting plasma insulin levels after glucose loading in young adult mice, as seen from the results of the oral glucose tolerance test. However, plasma glucose and insulin levels remained unchanged at the end of the experimental period. In conclusion, these results strongly suggest that the health-beneficial effects of BE may alter in mice at different life stages.

Dietary flaxseed oil induces production of adiponectin in visceral fat and prevents obesity in mice.

Induction of obesity by dietary fats and oils differs according to the type of fat. Adiponectin is believed to be related to obesity prevention. We hypothesized that flaxseed oil is important for preventing obesity and producing adiponectin. To clarify this hypothesis, we investigated the relationship between obesity and different fat sources in mice fed diets with 6 types of fat and oils. C57BL/6J mice were given a control diet containing 5% corn oil or a high-fat diet containing 20% of either lard, palm oil, rapeseed oil, oleate-rich safflower oil, corn oil, or flaxseed oil for 14 weeks. In another experiment, mice were given a control diet and rosiglitazone (10 mg/kg body weight) by oral gavage for 1 week. At the end of study, plasma adiponectin and expression of fatty acid metabolism-related factors in white and brown adipose tissue and the liver were measured. Dietary flaxseed oil, which is rich in α-linolenic acid, did not induce obesity. Flaxseed oil resulted in increased ß-oxidation-related factors in epididymal white adipose tissue, decreased fatty acid synthesis-related factors in the liver, and thermogenesis-related factor in brown adipose tissue following increase of plasma adiponectin. The results suggested that increase in plasma adiponectin after intake of flaxseed oil may be due to altered expression of AdipoQ and peroxisome proliferator-activated receptor γ in epididymal white adipose tissue. Flaxseed oil increased expression of adiponectin in visceral fat and regulated obesity-controlling fatty acid metabolism-related factors in white adipose tissue and liver, and thermogenesis-related factor in brown adipose tissue.

Mung bean peptides promote glucose uptake via Jak2 activation in L6 myotubes.

Mung beans are among the important edible legumes cultivated in Asia, Southern Europe, and Northern America. Mung beans contain 20-30% proteins with high digestibility and possess biological activities, but detailed health beneficial functions are not fully understood yet. In this study, we report the isolation and identification of active peptides from mung beans which promote glucose uptake and elucidate their mechanism in L6 myotubes. HTL, FLSSTEAQQSY, and TLVNPDGRDSY were isolated and identified as active peptides. These peptides promoted the translocation of glucose transporter 4 (GLUT4) to the plasma membrane. The tripeptide HTL promoted glucose uptake through the activation of adenosine monophosphate-activated protein kinase, while the oligopeptides FLSSTEAQQSY and TLVNPDGRDSY through the activation of the PI3K/Akt pathway. Furthermore, these peptides promoted the phosphorylation of Jak2 via interaction with the leptin receptor. Thus, mung bean is a promising functional food for the prevention of hyperglycemia and type 2 diabetes through promoting glucose uptake accompanied by JAK2 activation in the muscle cells.

Bacillus velezensis S141, a soybean growth-promoting bacterium, hydrolyzes isoflavone glycosides into aglycones.

Bacillus velezensis S141, a plant growth-promoting rhizobacteria (PGPR), was isolated from a soybean field in Thailand. Previous studies demonstrated that S141 enhanced soybean growth, stimulating nodulation for symbiotic nitrogen fixation with soybean root nodule bacteria, including Bradyrhizobium diazoefficience USDA110. Isoflavone glycosides are produced in soybean roots and hydrolyzed into their aglycones, triggering nodulation. This study revealed that S141 efficiently hydrolyzed two isoflavone glycosides in soybean roots (daidzin and genistin) to their aglycones (daidzein and genistein, respectively). However, S141, Bacillus subtilis 168, NCIB3610, and B. velezensis FZB42 hydrolyzed isoflavone glucosides into aglycones. A BLASTp search suggested that S141 and the other three strains shared four genes encoding ß-glucosidases corresponding to bglA, bglC, bglH, and gmuD in B. subtilis 168. The gene inactivation analysis of B. subtilis 168 revealed that bglC encoded the major ß-glucosidase, contributing about half of the total activity to hydrolyze isoflavone glycosides and that bglA, bglH, and gmuD, all barely committed to the hydrolysis of isoflavone glycosides. Thus, an unknown ß-glucosidase exists, and our genetic knowledge of ß-glucosidases was insufficient to evaluate the ability to hydrolyze isoflavone glycosides. Nevertheless, S141 could predominate in the soybean rhizosphere, releasing isoflavone aglycones to enhance soybean nodulation.

Aged Garlic Extract Prevents Alcohol-Induced Cytotoxicity through Induction of Aldehyde Dehydrogenase 2 in the Liver of Mice.

SCOPE: Acetaldehyde is a highly toxic primary metabolite of ethanol, and converts to nontoxic acetic acid by aldehyde dehydrogenase (ALDH). Accumulation of acetaldehyde causes significant damage to human body. Aged garlic extract (AGE) is a functional food material and possesses various health beneficial effects. This study investigates whether AGE contributes to acetaldehyde detoxification through ALDH induction and its underlying mechanism. METHODS AND RESULTS: C57BL/6J mice are orally administrated 10-1000 mg kg-1 body weight (BW) of AGE for 1 week before ethanol administration. AGE suppresses ethanol-caused accumulation of acetaldehyde level in the plasma through inducing mitochondrial ALDH2 but not cytosolic ALDH1A1. AGE also induces antioxidant enzymes, heme oxygenase-1, and NAD(P)H:quinone oxidoreductase 1, resulting in prevention of lipid peroxidation in the liver. In HepG2 cells, AGE prevents ethanol- and acetaldehyde-caused cytotoxicity. AGE induces mitochondrial ALDH2 through activating nuclear factor-erythroid 2-related factor 2 (Nrf2). AGE inhibits protein degradation of Nrf2 and enhances protein degradation of kelch-like ECH-associated protein 1. Furthermore, S-allyl cysteine and S-allyl mercaptocysteine as the bioactive compounds in AGE also induce ALDH2 and Nrf2. CONCLUSION: AGE prevents acetaldehyde-induced hepatotoxicity through enhancing acetaldehyde detoxification through Nrf2-dependent induction of mitochondrial ALDH2.

Development of sandwich ELISAs for detecting glucagon-like peptide-1 secretion from intestinal L-cells and their application in STC-1 cells and mice.

Certain nutrients stimulate glucagon-like peptide-1 (GLP-1) secretion from the intestinal enteroendocrine L-cells, but due to rapid degradation by the DPP-4 enzyme, >90% is converted to inactive metabolite before reaching the target organs via circulation. Plants are a source of potent bioactive compounds that promote endogenous secretion of GLP-1 from L-cells. To search for the effective bioactive compound from a vast library of natural compounds, a reliable and low-cost assay is required considering the high cost of commercial assays. We developed a low-cost sandwich enzyme-linked immunosorbent assays (s-ELISAs) for detecting 'total', 'sensitive active', and 'wide-range active' GLP-1. The s-ELISAs exhibited high sensitivity with measurement ranges between 0.94~240, 0.98~62.5, and 4.8~4,480 pmol/L, respectively. High precision was observed; i.e., CVs within 5% and 20% for intra- and inter-assay variations, respectively, and excellent recovery of exogenous GLP-1 from assay buffer. The developed s-ELISAs had the same performance as the commercial kits and approximately 80% cheaper cost. For their application, cinnamtannin A2-induced GLP-1 secretion was confirmed in STC-1 cells consistent with our previous findings. The s-ELISAs were further validated by measuring plasma GLP-1 level in mice after oral administration of black soy bean seed coat extract containing cinnamtannin A2.

Black soybean seed coat polyphenol ameliorates the abnormal feeding pattern induced by high-fat diet consumption.

High-fat diet (HFD) consumption induces chronic inflammation and microglial accumulation in the mediobasal hypothalamus (MBH), the central regulator of feeding behavior and peripheral metabolism. As a result, the diurnal feeding rhythm is disrupted, leading to the development of obesity. Diet-induced obesity (DIO) can be prevented by restoring the normal feeding pattern. Therefore, functional foods and drugs that ameliorate hypothalamic inflammation and restore the normal feeding pattern may prevent or ameliorate DIO. Numerous functional foods and food-derived compounds with anti-obesity effects have been identified; however, few studies have been performed that assessed their potential to prevent the HFD-induced hypothalamic inflammation and disruption of feeding rhythm. In the present study, we found that polyphenols derived from black soybean seed coat (BE) significantly ameliorated the accumulation of activated microglia and pro-inflammatory cytokine expression in the arcuate nucleus of the hypothalamus of HFD-fed mice, and restored their feeding pattern to one comparable to that of standard diet-fed mice, thereby ameliorating DIO. Furthermore, cyanidin 3-O-glucoside-the principal anthocyanin in BE-was found to be a strong candidate mediator of these effects. This is the first study to show that BE has the potential to provide a variety of beneficial effects on health, which involve amelioration of the HFD-induced hypothalamic inflammation and abnormal feeding pattern. The results of this study provide new evidence for the anti-obesity effects of black soybean polyphenols.

Vitamin E functions by association with a novel binding site on the 67 kDa laminin receptor activating diacylglycerol kinase.

It is generally recognized that the main function of α-tocopherol (αToc), which is the most active form of vitamin E, is its antioxidant effect, while non-antioxidant effects have also been reported. We previously found that αToc ameliorates diabetic nephropathy via diacylglycerol kinase alpha (DGKα) activation in vivo, and the activation was not related to the antioxidant effect. However, the underlying mechanism of how αToc activates DGKα have been enigmatic. We report that the membrane-bound 67 kDa laminin receptor (67LR), which has previously been shown to serve as a receptor for epigallocatechin gallate (EGCG), also contains a novel binding site for vitamin E, and its association with Vitamin E mediates DGKα activation by αToc. We employed hydrogen-deuterium exchange mass spectrometry (HDX/MS) and molecular dynamics (MD) simulations to identify the specific binding site of αToc on the 67LR and discovered the conformation of the specific hydrophobic pocket that accommodates αToc. Also, HDX/MS and MD simulations demonstrated the detailed binding of EGCG to a water-exposed hydrophilic site on 67LR, while in contrast αToc binds to a distinct hydrophobic site. We demonstrated that 67LR triggers an important signaling pathway mediating non-antioxidant effects of αToc, such as DGKα activation. This is the first evidence demonstrating a membrane receptor for αToc and one of the underlying mechanisms of a non-antioxidant function for αToc.

Pectolinarigenin Induces Antioxidant Enzymes through Nrf2/ARE Pathway in HepG2 Cells.

Pectolinarigenin (PG) and its glycoside pectolinarin (PN) were reported to have various health beneficial functions such as anti-inflammatory and anti-carcinogenic activities. It has also been reported that PG and PN have radical scavenging ability as direct antioxidant activity. However, the indirect antioxidant activity of PG and PN by inducing antioxidant enzymes in hepatocytes is not fully understood yet. In this study, we investigated whether PG and PN increase expression of antioxidant enzymes through the nuclear factor-erythroid-2-related factor 2 (Nrf2)-mediated pathway in human hepatoma HepG2 cells and the liver of male ICR mice. PG, but not PN, induced antioxidant enzymes, namely heme oxigenase-1, NAD(P)H:quinone oxidoreductase 1, and aldo-keto reductase family 1 member B10, in HepG2 cells. As for the induction mechanism of these enzymes, PG-induced nuclear accumulation of Nrf2 increased antioxidant response element (ARE)-mediated transcriptional activity and suppressed degradation of Nrf2 through modification of Kelch-like EXH-associated protein 1. Oral administration of PG also induced nuclear accumulation Nrf2 and expression of antioxidant enzymes in the liver of mice. Therefore, PG, but not PN, exhibits the indirect antioxidant activity by inducing antioxidant enzymes through the Nrf2/ARE pathway and may protect liver from oxidative stress.

Phenylpropanoids and neolignans isolated from Myristica fragrans enhance glucose uptake in myotubes.

Nutmeg is the seed of Myristica fragrans or its powder and is used as a spice and a traditional medicine. The antidiabetic effect of nutmeg is not fully understood yet. In this study, we examine the isolation and identification of the active compounds of Myristica fragrans with regards to glucose uptake and elucidate their mechanism in L6 myotubes. Myrisiticin, licarin B, erythro-2-(4-allyl-2,6-dimethoxy-phenoxy)-1-(3,4-dimethoxyphenyl)-propan-1-ol (ADDP) and (7S,8R)-2-(4-allyl-2,6-dimethoxyphenoxy)-1-(3,4,5-trimethoxyphenyl)-propan-1-ol (ADTP) were isolated and identified as the active compounds. Myristicin or a mixture of ADDP and ADTP promoted the translocation of glucose transporter 4 (GLUT4) through phosphorylation of AMP-activated protein kinase in L6 myotubes 15 min after treatment, while licarin B promoted it 240 min after treatment. Oral administration of the fraction from Myristica fragrans containing these active compounds to ICR mice suppressed post-prandial hyperglycemia. Thus, Myristica fragrans is a promising functional food to prevent post-prandial hyperglycemia and type 2 diabetes mellitus by promoting glucose uptake in muscle.

Preventive effects of black soybean polyphenols on non-alcoholic fatty liver disease in three different mouse models.

Non-alcoholic fatty liver disease (NAFLD) and its advanced stage, non-alcoholic steatohepatitis (NASH), are a major health issue throughout the world. Certain food components such as polyphenols are expected to possess preventive effects on NAFLD and NASH. In this study, the preventive effects of black soybean polyphenols were examined by using three NAFLD/NASH animal models. In a choline-deficient and L-amino acid-defined high-fat diet-induced NASH model, the intake of black soybean polyphenols decreased oxidative stress, but failed in attenuating liver injury and decreasing the expression of alpha-smooth muscle actin (α-SMA). In a Western diet with sucrose and fructose containing sweetened water-induced NAFLD model, black soybean polyphenols suppressed hepatic lipid accumulation, oxidative stress, aminotransferase activities in the plasma, inflammatory cytokine expression, and α-SMA expression accompanied by modulation of lipid metabolism. In a combination of Western diet and carbon tetrachloride model, black soybean polyphenols also suppressed hepatic lipid accumulation, oxidative stress, aminotransferase activities in the plasma, and α-SMA expression. In conclusion, black soybean is an attractive food for the prevention of NAFLD and NASH due to its strong antioxidant activity.

Theobromine enhances the conversion of white adipocytes into beige adipocytes in a PPARγ activation-dependent manner.

The adipocytes play an important role in driving the obese-state-white adipose tissue (WAT) stores the excess energy as fat, wherein brown adipose tissue (BAT) is responsible for energy expenditure via the thermoregulatory function of uncoupling protein 1 (UCP1)-the imbalance between these two onsets obesity. Moreover, the anti-obesity effects of brown-like-adipocytes (beige) in WAT are well documented. Browning, the process of transformation of energy-storing into energy-dissipating adipocytes, is a potential preventive strategy against obesity and its related diseases. In the present study, to explore an alternative source of natural products in the regulation of adipocyte transformation, we assessed the potential of theobromine (TB), a bitter alkaloid of the cacao plant, inducing browning in mice (in vivo) and primary adipocytes (in vitro). Dietary supplementation of TB significantly increased skin temperature of the inguinal region in mice and induced the expression of UCP1 protein. It also increased the expression levels of mitochondrial marker proteins in subcutaneous adipose tissues but not in visceral adipose tissues. The microarray analysis showed that TB supplementation upregulated multiple thermogenic and beige adipocyte marker genes in subcutaneous adipose tissue. Furthermore, in mouse-derived primary adipocytes, TB upregulated the expression of the UCP1 protein and mitochondrial mass in a PPARγ ligand-dependent manner. It also increased the phosphorylation levels of PPARγ coactivator 1α without affecting its protein expression. These results indicate that dietary supplementation of TB induces browning in subcutaneous WAT and enhances PPARγ-induced UCP1 expression in vitro, suggesting its potential to treat obesity.

5-Aminolevulinic acid combined with ferrous iron improves glucose tolerance in high-fat diet-fed mice via upregulation of glucose transporter 1.

Decreased mitochondrial metabolism suppresses glucose metabolism, resulting in obesity and diabetes. The present study aimed to investigate mechanisms underlying the 5-aminolevulinic acid (5-ALA) hydrochloride-mediated increase in glucose uptake in high-fat diet (HFD)-fed mice in vivo and C2C12 myotube cells in vitro. C57BL/6N male mice (20 weeks old) were fed either HFD or normal diet (ND) for 4 weeks. A total of five HFD-fed mice were orally administered with 300 mg/kg 5-ALA hydrochloride and 47.1 mg/kg sodium ferrous citrate (SFC; HFD + 5-ALA/SFC), whereas ND and other HFD-fed mice were orally administered with saline. After 4 weeks, these mice were intraperitoneally administered with 2 g/kg glucose and 3.2 mg/kg 2-deoxyglucose (2DG) for intraperitoneal glucose tolerance test (IPGTT) and glucose uptake test. Body weights, plasma glucose levels and the area under the curve of IPGTT were lower in mice treated with HFD + 5-ALA/SFC compared with in those treated with HFD alone. 2DG uptake in the gastrocnemius muscle and heart were more significantly improved in the HFD + 5-ALA/SFC mice compared with the HFD-fed mice. Furthermore, 5-ALA/SFC increased 2DG uptake in C2C12 cells to a similar level to the insulin-treated group. Moreover, it increased glucose transport (GLUT)1 translocation in the plasma membrane by 2.5-fold relative to the controls without affecting GLUT1 expression; however, it had no effect on GLUT4 translocation. Therefore, 5-ALA/SFC enhanced gastrocnemius and cardiac glucose uptake in HFD-fed mice, and upregulated GLUT1 translocation to the plasma membrane, but not GLUT4 in C2C12 myotube cells. Therefore, it could potentially be used as a novel drug for the treatment of diabetes.

Kaempferol Promotes Glucose Uptake in Myotubes through a JAK2-Dependent Pathway.

Kaempferol possesses various health-promoting functions including antihyperglycemic activity, but its underlying molecular mechanism is poorly understood. Glucose transporter 4 (GLUT4) plays an important role in the uptake of blood glucose into muscle cells after its translocation to the plasma membrane. In this study, we demonstrated that kaempferol at 1.0 nM or more significantly increased the uptake of 2-[3H]- deoxy-d-glucose by 1.3-1.4-fold in L6 myotubes. Kaempferol at 10 pM or more also significantly increased GLUT4 translocation by 1.3-1.6-fold. Kaempferol at 1.0 nM significantly increased the phosphorylation of adenosine monophosphate-activated protein kinase (AMPK) by 2.9-fold, liver kinase B1 and Janus kinase 2 (JAK2) by 1.9-fold, and signal transducer and activator of transcription 3 by 3.7-fold. In addition, kaempferol increased phosphorylation of phosphoinositide 3-kinase (PI3K) by 1.8-fold but not the insulin receptor. Small interfering RNA (siRNA) for AMPK, JAK2, or PI3K canceled kaempferol-induced glucose uptake and GLUT4 translocation. Furthermore, siRNA for JAK2 canceled kaempferol-induced phosphorylation of AMPK and PI3K. These results indicate that a JAK2-depdendent pathway regulates kaempferol-induced glucose uptake and GLUT4 translocation in L6 myotubes and that kaempferol may be an effective compound for the prevention of hyperglycemia.

Black Soybean Improves Vascular Function and Blood Pressure: A Randomized, Placebo Controlled, Crossover Trial in Humans.

Vascular dysfunction and injurious stimuli such as oxidative stress are closely related to the risk of cardiovascular diseases (CVD). Dietary polyphenols are reported to exert beneficial effects in reducing the risk of CVD. Black soybean has been used as a nutritionally rich food and contains abundant polyphenols in its seed coat and grain. Black soybean has many beneficial physiological activities, and its prevention effects on CVD risk were reported mainly in animal experiments. In this study, we performed a randomized, single blind, placebo controlled, crossover trial to investigate the effect of black soybean consumption on the vascular function in healthy humans. Twenty-two healthy adults aged from 30 to 60 completed the four week trial with daily consumption of about a 40 g test material cookie containing 20 g roasted black soybean powder. Body composition, vascular function, biomarkers for oxidative stress, and polyphenol contents in the urine and the plasma were measured. After ingestion of the black soybean cookie, vascular function, which was evaluated by plethysmogram using a Pulse Analyzer®, was improved and systolic blood pressure was decreased. Moreover, nitric oxide levels in plasma and urine were increased, while an oxidative stress biomarker, 8-hydroxy-2'-deoxyguanosine level, in the plasma was decreased accompanied by an increase in the concentration of polyphenols derived from black soybean in plasma and urine. These results suggest that the antioxidant activity of black soybean polyphenols and an increase in the nitric oxide level may contribute to the improvement of vascular function. Thus, black soybean is an attractive food material for improvement of vascular function through decreasing oxidative stress by its potent antioxidant activity and increasing the nitric oxide level in healthy humans.

Insights into the potential benefits of black soybean (Glycine max L.) polyphenols in lifestyle diseases.

Black soybean (Glycine max L.), a cultivar containing abundant polyphenols in its seed coat such as anthocyanins and flavan-3-ols, has been reported to possess various health benefits toward lifestyle diseases. In this review article, the safety evaluation of polyphenol-rich black soybean seed coat extract (BE) and absorption of BE polyphenols are summarized. Additionally, we describe the antioxidant activity of BE polyphenols and their ability to induce antioxidant enzymes. The health benefits of BE and its polyphenols, such as anti-obesity and anti-hyperglycemic activities through the activation of AMP-activated protein kinase and translocation of glucose transporter 4, respectively, are also discussed. Furthermore, we found that black soybean polyphenols were involved in the improvement of vascular function. These emerging data require further investigation in scientific studies and human trials to evaluate the prevention of lifestyle diseases using black soybean polyphenols.

Enzymatically synthesized glycogen protects inflammation induced by urban particulate matter in normal human epidermal keratinocytes.

Urban particulate matters (PM) exposure is significantly correlated with extrinsic skin aging signs and skin cancer incidence. PM contains polycyclic aromatic hydrocarbons, and they act as the agonists of aryl hydrocarbon receptor (AhR). Activation of AhR promotes generation of intracellular reactive oxygen species (ROS) and inflammation. Enzymatically synthesized glycogen (ESG), which is synthesized from starch, possesses various functions, such as anti-tumor, anti-obesity and antioxidant. However, the effects of ESG on PM-induced skin inflammation remain unclear. In this study, we investigated whether ESG has a protective effect on PM-induced oxidative stress and inflammation in human epidermal keratinocytes. ESG inhibited PM-induced expression of inflammatory cytokines IL6, TNFA and PTGS2. ESG also inhibited PM-induced phosphorylation of MAPKs and ROS accumulation. However, ESG had no effect on PM-induced expression of CYP1A1, one of the target proteins of AhR. On the other hand, ESG increased nuclear translocation of Nrf2 and expression of antioxidant proteins, HO-1 and NQO1. These results suggest that ESG suppressed PM-induced inflammation by decreasing ROS accumulation through the Nrf2 pathway.