Hitoshi Ashida

Kobe University, Kōbe, Hyōgo, Japan

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Publications (195)397.12 Total impact

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    ABSTRACT: Soy beta-conglycinin (beta CG) consumption has been shown to improve insulin resistance and suppress diet-induced obesity. These physiological effects seem to be mediated by the normalization of adiponectin and insulin sensitivity. Here, we show that artificial enzyme-hydrolyzed beta CG peptides promote uptake of 2-deoxyglucose, a glucose analogue, accompanied by translocation of glucose transporter 4 in skeletal L6 myotubes. Inhibition of AMP-activated protein kinase (AMPK) attenuated beta CG peptides-induced glucose uptake activity, while inhibition of both insulin and nitrogen monoxide signaling did not affect the glucose uptake activity. Taken together, these results indicate that beta CG peptides directly induced glucose uptake through the AMPK signaling pathway in muscle cells and might function to prevent insulin resistance.
    No preview · Article · Sep 2015 · Food Science and Technology Research
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    ABSTRACT: Tea catechins promote glucose uptake in skeletal muscle cells. In this study, we investigated whether the addition of an acyl group to the C-3 position of catechins to generate 3-O-acyl-catechins promoted glucose uptake in L6 myotubes. 3-O-Myristoyl-(-)-epicatechin (EC-C14) and 3-O-palmitoyl-(-)-epicatechin (EC-C16) promoted glucose uptake and translocation of glucose transporter (GLUT) 4 in the cells. The effect of 3-O-acyl-(-)-epicatechins was stronger than that of (-)-epicatechin (EC), whereas neither 3-O-myristoyl-(+)-catechin (C-C14) nor 3-O-palmitoyl-(+)catechin (C-C16) promoted glucose uptake or GLUT4 translocation as well as (+)-catechin (C). We further investigated an affinity of catechins and 3-O-acyl-catechins to the lipid bilayer membrane by using surface plasma resonance analysis. Maximum binding amounts of EC-C16 and C-C16 to the lipid bilayer clearly increased compared with that of (-)-EC and (+)-C, respectively. We also examined the mechanism of GLUT4 translocation and found EC-C14 and EC-C16 induced the phosphorylation of PI3K, but did not affect phosphorylation of Akt or IR. In conclusion, the addition of an acyl group to the C-3 position of (-)-EC increases its affinity for the lipid bilayer membrane and promotes GLUT4 translocation through PI3K-dependent pathways in L6 myotubes.
    Preview · Article · Jul 2015 · International Journal of Molecular Sciences
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    ABSTRACT: Prostate cancer grows under hypoxic conditions. Hypoxia decreases androgen receptor (AR) protein levels. However, the molecular mechanism remains unclear. Here, we report that p62-mediated autophagy degrades AR protein and suppresses apoptosis in prostate cancer LNCaP cells in hypoxia. In LNCaP cells, hypoxia decreased AR at the protein level, but not at the mRNA level. Hypoxia-induced AR degradation was inhibited not only by knockdown of LC3, a key component of the autophagy machinery, but also by knockdown of p62. Depletion of p62 enhanced hypoxia-induced poly(ADP-ribose) polymerase cleavage and caspase-3 cleavage, markers of apoptosis, whereas simultaneous knockdown of p62 and AR suppressed hypoxia-induced apoptosis. Hypoxia increased the formation of a cytosolic p62-AR complex and enhanced sequestration of AR from the nucleus. Formation of this complex was promoted by the increased phosphorylation of serine 403 in the ubiquitin-associated domain of p62 during hypoxia. An antioxidant and an AMP-activated protein kinase (AMPK) inhibitor reduced hypoxia-induced p62 phosphorylation at serine 403 and suppressed hypoxia-induced complex formation between AR and p62. These results demonstrate that hypoxia enhances the complex formation between p62 and AR by promoting phosphorylation of p62 at serine 403, probably through activating AMPK, and that p62-mediated autophagy degrades AR protein for cell survival in hypoxia. Copyright © 2015. Published by Elsevier Inc.
    No preview · Article · Jul 2015 · Cellular Signalling
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    ABSTRACT: To develop a functional food for improvement and/or prevention of diabetic nephropathy, we investigated whether catechins can activate DGKα, which is involved in the vitamin E-induced improvement of diabetic renal dysfunction. Among the catechins tested, (-)-epicatechin-3-gallate, (-)-epigallocatechin-3-gallate (EGCg), (-)-catechin-3-gallate and (-)-gallocatechin-3-gallate induced DGKα translocation from the cytoplasm to the plasma membrane, which is an index of DGKα activation. In contrast, (-)-epicatechin, (-)-epigallocatechin and gallic acid did not induce the translocation. Among the four galloylated catechins, EGCg was most effective, dose-dependent and subtype-specific among type I DGKs. Importantly, EGCg did indeed up-regulate DGKα activity. In addition, we found that a 67 kDa laminin receptor (67LR) mediates the EGCg-induced activation of DGKα, and both 67LR and DGKα are expressed in podocyte among glomerular cells. Finally, the EGCg-induced translocation of DGKα was confirmed in cultured podocytes. Thus, EGCg activates DGKα via 67LR, providing the possibility that EGCg may improve and/or prevent diabetic renal dysfunction.
    Full-text · Article · May 2015 · Journal of Functional Foods
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    ABSTRACT: We previously reported that the intake of black tea promotes translocation of the insulin-sensitive glucose transporter (GLUT) 4 in skeletal muscle. In this study, we investigated whether black tea polyphenols (BTP) promote GLUT4 translocation in L6 myotubes. BTP promoted glucose uptake accompanied by GLUT4 translocation in L6 myotubes. As the molecular mechanism, BTP induced the phosphorylation of insulin receptor substrate-1, atypical protein kinase C, Akt Thr308, Akt substrate 160, and AMP-activated protein kinase (AMPK), but did not affect that of Akt Ser473. BTP increased glycogen accumulation through inactivation of glycogen synthase kinase 3β (GSK-3β). Theaflavin, one of the major components in black tea, also promoted the glucose uptake accompanied by GLUT4 translocation observed with BTP in L6 myotubes. These results indicate that BTP activates both PI3K-and AMPKdependent pathways to promote GLUT4 translocation and glycogen accumulation in skeletal muscle cells. Moreover, theaflavin is one of the active components in BTP.
    No preview · Article · May 2015 · Food Science and Technology Research
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    ABSTRACT: Abstract Polycyclic aromatic hydrocarbons (PAHs) and halogenated aromatic hydrocarbons (HAHs) develop various adverse effects through activation of an aryl hydrocarbon receptor (AhR). The suppressive effects of brewed green tea and black tea on 3-methylcholanthrene (MC)-induced AhR activation and its downstream events were examined in the liver of rats. Ad-libitum drinking of green tea and black tea suppressed MC-induced AhR activation and elevation of ethoxyresorufin O-deethylase activity in the liver, whereas the teas themselves did not induce them. Tea showed a suppressive fashion on the expression of cytochrome P450 1A1 (CYP1A1). Tea suppressed the AhR activation induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) ex vivo. A part of catechins and theaflavins was present in plasma and liver as conjugated and intact forms. The results of this study suggested that active component(s) of tea are incorporated in the liver and suppress the activity of CYP1As through the AhR activation pathway.
    Full-text · Article · Jan 2015 · International Journal of Food Sciences and Nutrition
  • Itsuko Fukuda · Hitoshi Ashida
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    ABSTRACT: Carcinogenicity induced by phase I and phase II drug-metabolizing enzymes (DMEs) involves the following: certain procarcinogens are metabolized and activated into carcinogens by phase I CYPs or phase II GSTs, and the resultant carcinogens bind with biological macromolecules; this is an initiation step of carcinogenicity. Conversely, multidrug resistance is caused by an overexpression of transporters excreting chemotherapeutic agents in cancer cells. Naturally occurring polyphenols have been reported to possess anticancer effects. In this review, strategies for preventing carcinogenicity involving DMEs and transporters by polyphenols are discussed. Regarding DMEs, the balance of phase I and phase II enzymes is important for preventing carcinogenicity, and tea polyphenols, flavonoids, curcumin and resveratrol are candidates for suppressing tumorigenesis. Tea polyphenols, flavonoids, resveratrol, tannic acid, and curcumin all inhibit, or modulate, ABC transporters, and could prevent multidrug resistance in cancer cells.
    No preview · Chapter · Dec 2014
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    ABSTRACT: 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) causes various toxic effects, including wasting syndrome, through activation of an aryl hydrocarbon receptor (AhR). Our previous report demonstrated that certain flavonoids inhibit the activation of AhR and suppress its DNA binding activity. In this study, we searched for an active compound among 13 flavonoids that suppressed TCDD-induced loss of lipid accumulation using 3T3-L1 adipocytes as a cell culture model for wasting syndrome. Two flavonoids, luteolin and epigallocatechin gallate, suppressed TCDD-induced loss of lipid accumulation in this model. We further investigated luteolin to clarify the underlying molecular mechanism and confirmed that luteolin inhibited nuclear translocation of AhR caused by TCDD. Luteolin also inhibited the TCDD-driven decrease in protein expression of peroxisome proliferator-activated receptor γ (PPARγ) and CCAAT/enhancer-binding protein α (C/EBPα). Although TCDD alone did not change protein expression of C/EBPβ and C/EBPδ, luteolin and TCDD up-regulated C/EBPδ expression in a dose-dependent manner. On the other hand, TCDD significantly decreased DNA binding of C/EBPβ and C/EBPδ, and luteolin completely canceled TCDD-decreased DNA binding of them. We conclude that luteolin suppresses the TCDD-induced loss of lipid accumulation in 3T3-L1 adipocytes by preventing a decrease in protein expression of PPARγ and C/EBPα, the master regulators of adipocyte differentiation and in DNA binding of C/EBPβ and C/EBPδ. Moreover, luteolin was rapidly incorporated and accumulated in 3T3-L1 adipocytes. Thus, luteolin is an attractive compound for the prevention of TCDD-induced wasting syndrome. Copyright © 2014 Elsevier Inc. All rights reserved.
    No preview · Article · Nov 2014 · Pesticide Biochemistry and Physiology
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    ABSTRACT: Two main chalcones, 4-hydroxyderricin and xanthoangelol, from Ashitaba, which is a food ingredient and a folk medicine in Asia, have been demonstrated to modulate lipid metabolism in 3T3-L1 and HepG2 cells. In this study, we investigated the effects of Ashitaba extract on adiposity in mice fed a high-fat (HF) diet and its underlying mechanisms based on adipose tissue and hepatic lipid metabolism. C57BL/6 mice were fed a normal or HF diet supplemented with Ashitaba extract (0.01% and 0.1%, w/w) for 16 weeks. Ashitaba extract suppressed the HF diet-induced body weight gain and fat deposition in white adipose tissue, reduced plasma cholesterol, glucose, and insulin levels, increased the adiponectin level, lowered triglyceride and the liver cholesterol content, increased phosphorylation of AMP-activated protein kinase (AMPK) in adipose tissue and liver, inhibited lipogenesis in adipose tissue by down-expression of peroxisome proliferator-activated receptor (PPAR) γ, CCAAT/enhancer-binding protein α and sterol regulatory element-binding protein 1 (SREBP1), inhibited lipogenesis in the liver by down-expression of SREBP1 and its target enzyme fatty acid synthase, and promoted fatty acid oxidation by up-expression of carnitine palmitoyltransferase-1A and PPARα. In conclusion, Ashitaba extract can possibly prevent adiposity through modulating lipid metabolism through phosphorylation of AMPK in adipose tissue and liver.
    Full-text · Article · Nov 2014 · Food & Function
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    ABSTRACT: It is well known that tea has a variety of beneficial impacts on human health, including anti-obesity effects. It is well documented that green tea and its constituent catechins suppress obesity, but the effects of other tea on obesity and its potential mechanisms involved are not yet fully understood. In this study, we investigated suppression of adiposity by oolong, black and pu-erh tea and characterized the underlying molecular mechanism in vivo. We found that consumption of oolong, black or pu-erh tea for a period of one week significantly decreased visceral fat without affecting body weight in male ICR mice. On a mechanistic level, consumption of tea increased phosphorylation of AMP-activated protein kinase (AMPK) in white adipose tissue (WAT). This was accompanied by the induction of WAT protein levels of uncoupling protein 1 and insulin-like growth factor binding protein 1. Our results indicate that oolong, black and pu-erh tea, in particular black tea, suppresses adiposity via phosphorylation of the key metabolic regulator AMPK and increases browning of WATs.
    No preview · Article · Jul 2014
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    ABSTRACT: Thioredoxin (TRX) is a redox regulating protein which has protective effects against oxidative stress-induced damage to cells and tissues. In this study, we investigated the effects of orally administered TRX derived from edible yeast, Saccharomyces cerevisiae, on gastric mucosa. First, we examined the digestibility of orally administered yeast TRX in mice, and detected yeast TRX in the stomach for 4 h after administration. Next, we investigated the mitigation of gastric mucosal injury after the oral administration of yeast TRX in water-immersion restraint stress and HCl/ethanol-induced gastric ulcer models. Furthermore, we conducted DNA microarray analysis, using the HCl/ethanol-induced model, which revealed that several groups of genes related to tissue repair were upregulated in ulcer regions in the stomachs of rats administered with yeast TRX. These results demonstrated the viability of the use of oral administrations of yeast TRX to protect the gastric mucosa.
    Full-text · Article · Jul 2014 · Bioscience Biotechnology and Biochemistry
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    ABSTRACT: Resveratrol (3,4',5-trihydroxy-trans-stilbene) is known to enhance the cytotoxicity of the anticancer drug doxorubicin. On the other hand, breast cancer MCF-7 cells acquire resistance to doxorubicin under hypoxic conditions. In this study, we investigated the effect of resveratrol on hypoxia-induced resistance to doxorubicin in MCF-7 cells. Resveratrol and its derivative 3,5-dihydroxy-4'-methoxy-trans-stilbene, but not 3,5-dimethoxy-4'-hydroxy-trans-stilbene, cancelled hypoxia-induced resistance to doxorubicin at a concentration of 10 μM. Carbonyl reductase 1 (CBR1) catalyzes the conversion of doxorubicin to its metabolite doxorubicinol, which is much less effective than doxorubicin. Hypoxia increased the expression of CBR1 at both mRNA and protein levels, and knockdown of CBR1 inhibited hypoxia-induced resistance to doxorubicin in MCF-7 cells. Knockdown of hypoxia-inducible factor (HIF)-1α repressed the hypoxia-induced expression of CBR1. Resveratrol repressed the expression of HIF-1α protein, but not HIF-1α mRNA, and decreased hypoxia-activated HIF-1 activity. Resveratrol repressed the hypoxia-induced expression of CBR1 at both mRNA and protein levels. Likewise, 3,5-dihydroxy-4'-methoxy-trans-stilbene decreased the hypoxia-induced expression of CBR1 protein, but not 3,5-dimethoxy-4'-hydroxy-trans-stilbene. Furthermore, resveratrol decreased the expression of HIF-1α protein even in the presence of the proteasome inhibitor MG132 in hypoxia. Theses results indicate that in MCF-7 cells, HIF-1α-increased CBR1 expression plays an important role in hypoxia-induced resistance to doxorubicin and that resveratrol and 3,5-dihydroxy-4'-methoxy-trans-stilbene decrease CBR1 expression by decreasing HIF-1α protein expression, perhaps through a proteasome-independent pathway, and consequently repress hypoxia-induced resistance to doxorubicin.
    No preview · Article · Jun 2014 · Journal of Nutritional Science and Vitaminology
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    ABSTRACT: The present study demonstrates that glabridin, a prenylated isoflavone in licorice, stimulates glucose uptake through the adenosine monophosphate-activated protein kinase (AMPK) pathway in L6 myotubes. Treatment with glabridin for 4 h induced glucose uptake in a dose-dependent manner accompanied by the translocation of glucose transporter type 4 (GLUT4) to the plasma membrane. Glabridin needed at least 4 h to increase glucose uptake, while it significantly decreased glycogen and increased lactic acid within 15 min. Pharmacological inhibition of AMPK by compound C suppressed the glabridin-induced glucose uptake, whereas phosphoinositide 3-kinase and Akt inhibition by LY294002 and Akt1/2 inhibitor, respectively, did not. Furthermore, glabridin induced AMPK phosphorylation, and siRNA for AMPK completely abolished glabridin-induced glucose uptake. We confirmed that glabridin-rich licorice extract prevent glucose intolerance accompanied by the AMPK-dependent GLUT4 translocation in the plasma membrane of skeletal muscle. These results indicate that glabridin may possess a therapeutic effect on metabolic disorders, such as diabetes and hyperglycemia, by modulating glucose metabolism through AMPK in skeletal muscle cells.
    No preview · Article · Jun 2014 · Molecular and Cellular Endocrinology
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    ABSTRACT: Unlabelled: Drugs, xenobiotics including environmental pollutants, and certain food components modulate expression of drug-metabolizing enzymes. An aryl hydrocarbon receptor (AhR) possesses possible expression of phase I and phase II enzymes directly by binding of its ligands such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and indirectly by regulating expression of nuclear factor-erythroid-2-related factor 2 (Nrf2). Previous our result demonstrated that luteolin, a natural flavonoid existing in vegetables and herbs, competed the binding of TCDD to AhR. In the present study, we investigated the effect of luteolin on the expression of drug-metabolizing enzymes through the AhR and Nrf2 pathways. Luteolin inhibited TCDD-induced protein expression of phase I enzyme cytochrome P450 1A1 (CYP1A1), phase II enzymes Nad(p)h: quinone oxidoreductase-1 (NQO1) and glutathione-S-transferase P1 (GSTP1) in HepG2, Hepa1c1c7 and RL-34 cells in a dose-dependent manner. Luteolin suppressed TCDD- and tert-butylhydroquinone-induced Nrf2 protein by decreasing its stability in HepG2 cells. In tert-butylhydroquinone treated cells, luteolin dose-dependently inhibited NQO1, GSTP1 and aldo-keto reductases (AKRs). Of these, protein expression of CYP1A1 and GSTP1 was mainly dominated by the AhR pathway, while that of NQO1 and AKRs was by the Nrf2 pathway. In conclusion, luteolin inhibits expression of phase I and phase II drug-metabolizing enzymes by modulating the AhR and Nrf2 pathways.
    No preview · Article · Jun 2014 · Archives of Biochemistry and Biophysics
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    ABSTRACT: We investigated whether rutin, a flavonoid isolated from Toona sinensis Roem, has the ability to enhance insulin-dependent receptor kinase (IRK) activity and glucose transporter 4 (GLUT4) translocation in differentiated myotubes. We also tested the effects of rutin treatment in insulin-resistant mice using an oral glucose tolerance test (OGTT). Rutin potentiated insulin receptor kinase (IRK) phosphorylation when IRK autophosphorylation was triggered by insulin in differentiated myotubes. Co-treatment of cells with rutin and insulin attenuated S961-mediated inhibition of insulin-dependent GLUT4 translocation. In S961-treated C57BL/6 mice, an in vivo model of insulin resistance and type 2 diabetes, rutin treatment showed a normoglycemic effect in the OGTT. This study shows evidence that rutin may serve as a potential agent for glycemic control through enhancement of IRK activity, thereby inducing the insulin signaling pathway causing increased GLUT4 translocation and increased glucose uptake.
    No preview · Article · Jun 2014 · Molecular Nutrition & Food Research
  • Tianshun Zhang · Norio Yamamoto · Yoko Yamashita · Hitoshi Ashida
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    ABSTRACT: Aim: We searched for polyphenols capable of inhibiting the lipid accumulation in 3T3-L1 cells, and investigated the mechanisms of two effective chalcones cardamonin and flavokawain B on differentiation of preadipocytes. Method and results: We treated 3T3-L1 cells with a panel of 46 polyphenols and measured intracellular lipid accumulation by Sudan II staining. Four of them, including cardamonin and flavokawain B, inhibited lipid accumulation. In the further study, cardamonin and flavokawain B inhibited lipid accumulation by downregulating the expression of CCAAT/enhancer binding protein (C/EBP)-β, C/EBPα, and peroxisome proliferator-activated receptor-γ (PPARγ) at both mRNA and protein levels. Cardamonin and flavokawain B also increased phosphorylation of extracellular signal-regulated kinase (ERK) in the early phase of adipocyte differentiation. PD98059, an ERK inhibitor, restored C/EBPβ, PPARγ expression and intracellular lipid accumulation in adipocytes. Moreover, cardamonin and flavokawain B also modulated the secretion of C-reactive protein, dipeptidyl peptidase IV, interleukin-6, tumor necrosis factor-α and fibroblast growth factor-21 in mature adipocytes. Conclusions: These results indicate that ERK activation and consequent downregulation of adipocyte-specific transcription factors are involved in the inhibitory effects of the chalcones cardamonin and flavokawain B on adipocyte differentiation. Moreover, cardamonin and flavokawain B are able to modulate secretion of adipokines in mature adipocytes.
    No preview · Article · May 2014 · Archives of Biochemistry and Biophysics
  • Tianshun Zhang · Norio Yamamoto · Hitoshi Ashida
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    ABSTRACT: Excessive lipid accumulation in the liver has been proposed to cause hyperlipidemia, diabetes and fatty liver disease. 4-Hydroxyderricin (4HD), xanthoangelol (XAG), cardamonin (CAR) and flavokawain B (FKB) are chalcones that have exhibited various biological effects against obesity, inflammation, and diabetes; however, little is known about the inhibitory effects of these chalcones on fatty liver disease. In the present study, we investigated the ability of 4HD, XAG, CAR, and FKB to reduce lipid accumulation in hepatocytes. When HepG2 cells were treated with a mixture of fatty acids (FAs; palmitic acid : oleic acid = 1 : 2 ratio), significant lipid accumulation was observed. Under the same experimental conditions, addition of chalcones at 5 μM significantly suppressed the FA-induced lipid accumulation. We found that the expression of sterol regulatory element-binding protein-1 (SREBP-1), a key molecule involved in lipogenesis, was decreased in these chalcone-treated cells. We also found that these chalcones increased the expression of peroxisome proliferator-activated receptor α (PPARα), which is involved in FA oxidation. Moreover, these chalcones increased phosphorylation of AMP-activated protein kinase (AMPK) and liver kinase B1 (LKB1), upstream regulators of SREBP-1 and PPARα. We confirmed that an AMPK inhibitor, compound C, reversed chalcone-induced changes in SREBP-1 and PPARα expression in the HepG2 cells. Collectively, we found that 4HD, XAG, CAR, and XAG attenuated lipid accumulation through activation of the LKB1/AMPK signaling pathway in HepG2 cells.
    No preview · Article · Apr 2014
  • Sayuri Shimazu · Masaya Ohta · Hitoshi Ashida
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    ABSTRACT: The aim of this study is to elucidate the effect of lipid extracts from Solidago canadensis for phytomonitoring of polychlorinated biphenyl (PCB) 126 in the transgenic Arabidopsis plant XgD2V11-6 carrying the recombinant guinea pig (g) aryl hydrocarbon receptor (AhR)-mediated β-glucuronidase (GUS) reporter gene expression system. A lipid extract was prepared from S. canadensis and separated into simple lipid, glycolipid, and phospholipid fractions by silica gel column chromatography. Sterylglucoside (SG), monogalactosyldiacylglycerol (MGDG), digalactosyldiacylglycerol (DGDG), and glucosyl ceramide were found in the glycolipid fraction. When the transgenic Arabidopsis plants were treated with the glycolipid fraction together with PCB126, PCB126-induced GUS activity significantly increased in the whole plant. Moreover, S. canadensis-derived SG, MGDG, and DGDG also significantly increased PCB126-induced GUS activity. These results indicated that glycolipids in S. canadensis enhanced the sensitivity of this monitoring assay.
    No preview · Article · Feb 2014 · Science of The Total Environment
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    ABSTRACT: Although the underlying mechanism is unclear, β-conglycinin (βCG), the major component of soy proteins, regulates blood glucose levels. Here, we hypothesized that consumption of βCG would normalize blood glucose levels by ameliorating insulin resistance and stimulating glucose uptake in skeletal muscles. To test our hypothesis, we investigated the antidiabetic action of βCG in spontaneously diabetic Goto-Kakizaki (GK) rats. Our results revealed that plasma adiponectin levels and adiponectin receptor 1 messenger RNA expression in skeletal muscle were higher in βCG-fed rats than in casein-fed rats. Phosphorylation of adenosine monophosphate-activated protein kinase (AMP kinase) but not phosphatidylinositol-3 kinase was activated in βCG-fed GK rats. Subsequently, βCG increased translocation of glucose transporter 4 to the plasma membrane. Unlike the results in skeletal muscle, the increase in adiponectin receptor 1 did not lead to AMP kinase activation in the liver of βCG-fed rats. The down-regulation of sterol regulatory element-binding factor 1, which is induced by low insulin levels, promoted the increase in hepatic insulin receptor substrate 2 expression. Based on these findings, we concluded that consumption of soy βCG improves glucose uptake in skeletal muscle via AMP kinase activation and ameliorates hepatic insulin resistance and that these actions may help normalize blood glucose levels in GK rats.
    No preview · Article · Feb 2014 · Nutrition research
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    ABSTRACT: The Japanese herb, Ashitaba (Angelica keiskei Koidzumi), contains two prenylated chalcones, 4-hydroxyderricin and xanthoangelol, which are considered to be the major active compounds of Ashitaba. However, their effects on inflammatory responses are poorly understood. In the present study, we investigated the effects and underlying molecular mechanisms of 4-hydroxyderricin and xanthoangelol on lipopolysaccharide (LPS)-induced inflammatory responses in RAW264 mouse macrophages. LPS-mediated production of nitric oxide (NO) was markedly reduced by 4-hydroxyderricin (10 μM) and xanthoangelol (5 μM) compared with their parent compound, chalcone (25 μM). They also inhibited LPS-induced secretion of tumor necrosis factor-alpha (TNF-α), and gene and protein expression of inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2). Although chalcone decreased the DNA-binding activity of both activator protein-1 (AP-1) and nuclear factor-kappa B (NF-κB), 4-hydroxyderricin and xanthoangelol suppressed only AP-1 and had no effect on NF-κB. On the other hand, all of the tested chalcones reduced the phosphorylation (at serine 536) level of the p65 subunit of NF-κB. 4-Hydroxyderricin and xanthoangelol may be promising for the prevention of inflammatory diseases.
    Full-text · Article · Dec 2013 · Journal of Agricultural and Food Chemistry

Publication Stats

4k Citations
397.12 Total Impact Points


  • 1970-2015
    • Kobe University
      • • Department of Agrobioscience
      • • Graduate School of Agricultural Science
      • • Department of Biofunctional Chemistry
      • • Faculty of Agriculture
      Kōbe, Hyōgo, Japan
  • 2009
    • University of Shizuoka
      • Institute for Environmental Sciences
      Shizuoka-shi, Shizuoka-ken, Japan