食品ペプチドの健康維持機能に関する研究

食機能の分析化学的究明に関する研究

緑茶の高機能化に関して、ビワ葉の有する高いポリフェノールオキシダーゼ活性を利用し、１時間以内での発酵茶の製造を達成する技術を開発したこと。

フラボノイド代謝物の生体利用性を解明した初めての成果である。

ヘスペリジン摂取が血圧上昇を有意に抑制し、その作用は血管での弛緩受容体発現によることをラットを用いて実証した成果である。

食品包材でのにおい成分の損失挙動の解明に関する研究

テアフラビン類が腸管膜バリアーを増強させる機構を解明した初めての成果である。

高分子素材中に存在する低分子物質の分布性をMADL-MSイメージング法によって明らかにした初めての分析化学的成果である。

Language：English   Publishing type：Research paper (scientific journal)  

DOI： https://doi.org/10.1021/acsomega.4c04524

Language：English   Publisher：Bioscience, Biotechnology and Biochemistry  

In a previous study, we developed a novel analytical method to directly and simultaneously detect taste- and odor-active compounds using graphite carbon black (GCB)-assisted laser desorption ionization mass spectrometry (LDI-MS). In this study, we aimed to evaluate food quality using a variety of soy sauces using the method to discriminate each product. Graphite carbon black-laser desorption ionization-mass spectrometry allowed the provision of hundreds of MS peaks derived from soy sauces in both positive and negative modes without any tedious sample pretreatments. Principal component analysis using the obtained MS peaks clearly distinguished three soy sauce products based on the manufacturing countries (Japan, China, and India). Moreover, this method identified distinct MS peaks for discrimination, which significantly correlated with their quantitative amounts in the products. Thus, GCB-LDI-MS analysis was established as a simple and rapid technique for food analysis, illustrating the chemical patterns of food products.

DOI： 10.1093/bbb/zbae034

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Authorship：Last author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

DOI： https://doi.org/10.1021/acs.jafc.3c07821

Repository Public URL： https://hdl.handle.net/2324/7343017

Language：English   Publishing type：Research paper (scientific journal)   Publisher：Scientific Reports  

The transport and accumulation of orally administered functional food-derived peptides in the brain
was not fully explored. Thus, in the present study, we aimed to provide critical evidence regarding
brain accumulation of a memory-improving soy dipeptide, Tyr-Pro, following oral administration.
Stable isotope-labeled Tyr-Pro (Tyr-[13C5,15N]Pro) was orally administered to male ICR mice at 10 or
100 mg/kg. Surprisingly, the intact labeled Tyr-Pro exhibited maximal plasma and brain levels 15 min
after administration (plasma: area under the curve [AUC 0–120 min], 1331 ± 267 pmol·min/mL-plasma;
brain: AUC 0–120 min of 0.34 ± 0.11 pmol·min/mg-dry brain, at 10 mg/kg). In addition, we detected labeled
Tyr-Pro in the brain parenchyma, indicating a validated blood–brain-barrier (BBB) transportability.
Moreover, we confirmed the preferable accumulation of Tyr-Pro in the hypothalamus, hippocampus,
and cortex with > 0.02 pmol/mg-tissue. In conclusion, we provided the first evidence that orally
administered Tyr-Pro at 10 mg/kg directly entered the blood circulation with an absorption ratio of
0.15%, of which 2.5% of Tyr-Pro was transported from the plasma to the mouse brain parenchyma.

DOI： 10.1038/s41598-023-44161-z

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Repository Public URL： https://hdl.handle.net/2324/7165074

Language：English   Publishing type：Research paper (scientific journal)   Publisher：Food and Function  

Recent studies have indicated that lactate acts as a signaling molecule in various tissues. We previously demonstrated that intake of an amino acid mixture combined with exercise synergistically induced beige adipocyte formation in inguinal white adipose tissue (iWAT) in mice. Moreover, plasma lactate levels remained significantly elevated in the amino acid mixture + exercise group even 16 h after exercise, indicating that a lactate-mediated pathway may be involved in the induction of beige adipocyte formation. Against this background, we hypothesized that oral intake of lactate would induce beige adipocyte formation via the lactate signaling pathway without exercise. Furthermore, if oral intake of lactate can produce the same effect as exercise, lactate might be used as a food-derived exercise replacement-factor. Oral intake of lactate (100 mM in drinking water) for 4 weeks significantly induced beige adipocyte formation in iWAT in mice as well as a significant elevation of lactate transporter (monocarboxylic acid transporter 1; MCT1) and lactate dehydrogenase B levels. Administration of lactate to adipocytes significantly increased reactive oxygen species (ROS) and superoxide levels and the NADH/NAD+ ratio. The induction of lactate-mediated uncoupling protein 1 (UCP1) expression and ROS production were significantly suppressed by antioxidant treatment or inhibition of MCT1. However, UCP1 induction was not significantly affected by the inhibition of lactate receptor (hydroxycarboxylic acid receptor 1). These findings suggest that lactate-mediated ROS production induces beige adipocyte formation, and thus oral intake of lactate may confer some benefits of exercise without the need to perform exercise.

DOI： 10.1039/d3fo03287f

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Repository Public URL： https://hdl.handle.net/2324/7165073

Language：English   Publishing type：Research paper (scientific journal)   Publisher：Communications Biology  

The sweet taste receptor plays an essential role as an energy sensor by detecting carbohydrates. However, the dynamic mechanisms of receptor activation remain unclear. Here, we describe the interactions between the transmembrane domain of the G protein-coupled sweet receptor subunit, TAS1R3, and allosteric modulators. Molecular dynamics simulations reproduced species-specific sensitivity to ligands. We found that a human-specific sweetener, cyclamate, interacted with the mouse receptor as a negative allosteric modulator. Agonist-induced allostery during receptor activation was found to destabilize the intracellular part of the receptor, which potentially interfaces with the Gα subunit, through ionic lock opening. A common human variant (R757C) of the TAS1R3 exhibited a reduced response to sweet taste, in support of our predictions. Furthermore, histidine residues in the binding site acted as pH-sensitive microswitches to modulate the sensitivity to saccharin. This study provides important insights that may facilitate the prediction of dynamic activation mechanisms for other G protein-coupled receptors.

DOI： 10.1038/s42003-023-04705-5

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Repository Public URL： https://hdl.handle.net/2324/7165050

Language：English   Publishing type：Research paper (scientific journal)  

Repository Public URL： https://hdl.handle.net/2324/7165040

Language：English   Publishing type：Research paper (scientific journal)  

There is no analytical system to directly and simultaneously detect taste- and odor-active compounds. Graphite
carbon black (GCB) nanoparticles, a chemical adsorbent for a variety of compounds, including gaseous molecules, which consists of
nanoparticles made from multilayered sheets of sp2-conjugated atomic carbon, have the characteristics required for a surface-assisted
laser desorption ionization−mass spectrometry (SALDI-MS) material. Thus, in this study, GCB-LDI-MS was developed for the
simultaneous detection of taste- and odor-active compounds. The proposed GCB-LDI-MS successfully detected volatile compounds,
including ethyl esters, alcohols, fatty acids, and aldehydes with up to 16 carbons (maximum carbon number of the tested
compounds), which could not be detected by conventional matrix-assisted-LDI-MS. Moreover, a series of taste-active compounds
(e.g., amino acids and sugars) and various volatile compounds (e.g., ethyl esters, aldehydes, alcohols, fatty acids, and lactones) as a
mixture in liquid samples were also detected by the present GCB-LDI-MS. Thus, the proposed simple and rapid detection technique
can digitize the analysis of flavor compounds, which provides an analytical concept for flavor scanning to evaluate the palatability of
food products.

DOI： doi.org/10.1021/acsanm.1c03890

Repository Public URL： https://hdl.handle.net/2324/6770278

Language：English   Publishing type：Research paper (scientific journal)   Publisher：Journal of Agricultural and Food Chemistry  

Here, the mechanism of vasorelaxant Mas receptor (MasR) expression elevated by hesperidin in spontaneously
hypertensive rats was investigated in human umbilical vein endothelial cells (HUVECs). HUVECs were cultured with 1 μM
hesperidin for 2 h, following the measurements of nitric oxide (NO) production and vasomotor-related receptors’ expression.
Hesperidin significantly promoted NO production (224.1 ± 18.3%, P < 0.01 vs control) in the HUVECs. Only the MasR expression
was upregulated (141.2 ± 12.5%, P < 0.05 vs control), whereas a MasR antagonist did not alter the hesperidin-induced NO
production. When a transient receptor potential vanilloid 1 (TRPV1) was knocked down by silencing RNA or Ca2+/calmodulindependent
kinase II (CaMKII) and p38 mitogen-activated protein kinase (p38 MAPK) were inhibited, the increased MasR
expression by hesperidin was abrogated. The inhibitions of CaMKII and endothelial NO synthase (eNOS) abolished the hesperidininduced
NO production. The structure−activity relationship analysis of flavonoids demonstrated that the B ring of the twisted
flavonoid skeleton with a hydroxy group at the 3′ position was a crucial factor for TRPV1 stimulation. Taken together, it was
demonstrated that hesperidin may stimulate TRPV1-mediated cascades, leading to the activation of two signaling axes, CaMKII/p38
MAPK/MasR expression and CaMKII/eNOS/NO production in HUVECs.

DOI： 10.1021/acs.jafc.2c04045

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Repository Public URL： https://hdl.handle.net/2324/6770273

Language：English   Publishing type：Research paper (scientific journal)   Publisher：Journal of Agricultural and Food Chemistry  

The Tyr-Pro (YP) dipeptide can serve as an adiponectin receptor 1 (AdipoR1) agonist. We thus investigated the
AdipoR1-agonistic potential of YP-related tripeptides in the soybean protein sequence. Among the 17 soybean candidate tripeptides,
those elongated at the C-terminus of YP (0.1 μM YPG, 140 ± 16%; 0.1 μM YPE, 141 ± 22%; 0.1 μM YPP, 145 ± 19%; 0.1 μM
YPQ, 143 ± 20%; p < 0.05) significantly promoted glucose uptake by L6 muscle myotubes, comparable to the effect of 0.1 μM
AdipoRon (163 ± 52%, p < 0.05). The knockdown of AdipoR1 expression in L6 cells abrogated this effect of YPG and YPP,
indicating that the two tripeptides had an AdipoR1 agonistic effect. CHARMM-GUI-aided molecular dynamics simulation in a
virtual phospholipid membrane revealed that YPG and YPP were stably positioned at the binding pockets of AdipoR1 (binding free
energy < −10 kcal/mol). These findings demonstrate that the tripeptides YPG and YPP, with AdipoR1 agonistic YP sequences, have
alternative adiponectin-like potential via their preferential binding to AdipoR1.

DOI： 10.1021/acs.jafc.2c02115

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Repository Public URL： https://hdl.handle.net/2324/6770271

Language：English   Publishing type：Research paper (scientific journal)   Publisher：Sensors  

A taste sensor with lipid/polymer membranes is attracting attention as a method to evaluate taste objectively. However, due to the characteristic of detecting taste by changes in membrane potential, taste sensors cannot measure non-charged bitter substances. Many foods and medicines contain non-charged bitter substances, and it is necessary to quantify these tastes with sensors. Therefore, we have been developing taste sensors to detect bitter tastes caused by non-charged substances such as caffeine. In previous studies, a sensor for detecting bitterness caused by caffeine and theobromine, theophylline, was developed, using a membrane modified with hydroxybenzoic acid (HBA) as the sensing part. The sensor was designed to form intramolecular hydrogen bonds (H-bonds) between the hydroxy group and carboxy group of HBA and to successively cause the intermolecular H-bonds between HBA and caffeine molecules to be measured. However, whether this sensing principle is correct or not cannot be confirmed from the results of taste sensor measurements. Therefore, in this study, we explored the interaction between HBA and caffeine by1H-nuclear magnetic resonance spectroscopy (NMR). By the1H NMR detection, we confirmed that both the substances interact with each other. Furthermore, the nuclear Overhauser effect (NOE) of intermolecular spatial conformation in solution was measured, by which 2,6-dihydroxybenzoic acid (2,6-DHBA) preferably interacted with caffeine via the H-bonding and stacking configuration between aromatic rings. Identifying the binding form of 2,6-DHBA to caffeine was estimated to predict how the two substances interact.

DOI： 10.3390/s22072592

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Repository Public URL： https://hdl.handle.net/2324/6770283

Language：English   Publishing type：Research paper (scientific journal)   Publisher：American Chemical Society  

The application of matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) imaging to quantitative analyses is restricted by the variability of MS intensity of the analytes in nonreproducible matrix crystals of tissues. To overcome this challenge, fluorescence-assisted spraying method was developed for a constant matrix amount employing an MS-detectable fluorescent reagent, rhodamine 6G (R6G), which was sprayed with the matrix. To form a homogeneous matrix crystal on the tissue section, a matrix solution, 1,5-diaminonaphthalene (10 mg/mL), containing R6G (40 μg/mL) and O-dinitrobenzene (O-DNB, 10 mg/mL) was sprayed until the desired constant fluorescent intensity was achieved. Compared with that obtained via conventional cycle-number-fixed spraying (relative standard deviation (RSD) = 18.8%), the reproducibility of the relative MS intensity of the analyte (ferulic acid (FA), RSD = 3.1%) to R6G was significantly improved by the fluorescence-assisted matrix spraying. This result indicated that R6G could be employed as an index of the matrix amount, as well as a MS normalizing standard. The proposed matrix spraying successfully quantified nifedipine (0.5–40 pmol/mm_2 in the positive mode, R_2 = 0.965) and FA (0.5–75 pmol/mm_2 in the negative mode, R_2 = 0.9972) in the kidney section of a rat. Employing the quantitative MALDI-MS imaging assay, FA, which accumulated in the kidney of the rat after 50 mg/kg was orally administered, was visually determined to be 3.5, 3.0, and 0.2 μmol/g tissue at 15, 30, and 60 min, respectively.

DOI： 10.1021/acs.analchem.1c03369

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CiNii Research

Repository Public URL： https://hdl.handle.net/2324/4772284

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Apart from the physiological effects of glyceollins, information regarding their tissue distribution is scarce in the literature. Thus, the aim of this study is to clarify the distribution of glyceollins in rat organs. Glyceollins I and III were orally administered to Sprague-Dawley rats (1.0 mg/kg) with daidzein as control, and their accumulations in organs were investigated by liquid chromatography-time-of-flight/mass spectrometry (LC-TOF/MS). Glyceollins accumulated in intact and conjugated forms in circulatory organs with a Tmax of 0.5 h, in the following order of descending preference: liver, kidney, heart, lung, soleus muscle, and abdominal aorta. The accumulation of hydrophobic glyceollin I was more than 1.5 times higher than that of III. In contrast, daidzein and hydroxy equol were detected only in the liver and kidneys at lower concentrations (1/100 times) than those of glyceollins. In conclusion, prenylated isoflavones, glyceollins, were preferentially distributed in circulatory organs as intact, sulfated, or glucuronidated forms up to 6 h after the intake.

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Language：English   Publishing type：Research paper (scientific journal)  

The aim of this study is to develop a dipeptide showing an adiponectin receptor 1 (AdipoR1) agonistic effect in skeletal muscle L6 myotubes. Based on the structure of the AdipoR1 agonist, AdipoRon, 15 synthetic dipeptides were targeted to promote glucose uptake in L6 myotubes. Tyr-Pro showed a significant increase in glucose uptake among the dipeptides, while other dipeptides, including Pro-Tyr, failed to exert this effect. Tyr-Pro induces glucose transporter 4 (Glut4) expression in the plasma membrane, along with adenosine monophosphate-activated protein kinase (AMPK) activation. In AdipoR1-knocked down cells, the promotion by Tyr-Pro was ameliorated, indicating that Tyr-Pro may directly interact with AdipoR1 as an agonist, followed by the activation ofAMPK/Glut4 translocation in L6 myotubes. Molecular dynamics simulations revealed that a Tyr-Pro molecule was stably positioned in the two potential binding pockets (sites 1 and 2) of the seven-transmembrane receptor, AdipoR1, anchored in a virtual 1- palmitoyl-2-oleoyl-phosphatidylcholine membrane. In conclusion, we demonstrated the antidiabetic function of the Tyr-Pro dipeptide as a possible AdipoR1 agonist.

Repository Public URL： http://hdl.handle.net/2324/4772819

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Language：English   Publishing type：Research paper (scientific journal)  

Repository Public URL： http://hdl.handle.net/2324/4772813

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OBJECTIVE: To clarify the pathogenesis of human atheroma, the origin of deposited lipids, the developmental mechanism of liponecrotic tissue, and the significance of the oxidation of phospholipids were investigated using mass spectrometry-aided
imaging and immunohistochemistry.
APPROACH AND RESULTS: Atherosclerotic lesions in human coronary arteries were divided into 3 groups: pathologic intimal thickening with lipid pool, atheroma with lipid core, and atheroma with necrotic core. The lipid pool and lipid core were characterized by the deposition of extracellular lipids. The necrotic core comprised extracellular lipids and liponecrotic tissue. The proportion of cholesteryl linoleate in cholesteryl linoleate+cholesteryl oleate fraction in the extracellular lipid and liponecrotic regions differed significantly from that of the macrophage foam cell–dominant region, and the plasma-derived components (apolipoprotein B and fibrinogen) were localized in the regions. The liponecrotic region was devoid of elastic and collagen fibers and accompanied by macrophage infiltration in the surrounding tissue. Non–oxidized phospholipid (Non-OxPL), OxPL, and Mox macrophages were detected in the three lesions. In the atheroma with lipid core and atheroma with necrotic core, non-OxPL tended to localize in the superficial layer, whereas OxPL was distributed evenly. Mox macrophages were colocalized with OxPL epitopes.
CONCLUSIONS: In human atherosclerosis, plasma-derived lipids accumulate to form the lipid pool of pathologic intimal thickening, lipid core of atheroma with lipid core, and necrotic core of atheroma with necrotic core. The liponecrotic tissue in
the necrotic core appears to be developed by the loss of elastic and collagen fibers. Non-OxPL in the accumulated lipids is oxidized to form OxPL, which may contribute to the lesion development through Mox macrophages

Repository Public URL： https://hdl.handle.net/2324/7169010

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Repository Public URL： http://hdl.handle.net/2324/4772814

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In this study, β-conglycinin (100 mg/kg) was orally administered to Wistar rats in order to identify peptides that may be derived from the protein in the blood. Plasma samples taken from the tail vein up to 8 h after admin- istration were analyzed by matrix-assisted laser desorption/ionization (MALDI) and liquid chromatography- time-of-flight (LC-TOF) mass spectrometry (MS). In total, 126 signals were detected by MALDI-MS. Among the signals, nine oligopeptides (SEL, KGPL, SILGA, DSEL, GDANI, SYFV, CLQSC, GEQPRPF, and LVINEGDA) were successfully identified as β-conglycinin-derived peptides by LC-TOF/MS at a plasma concentration of 0.75–756 pmol/mL. The results demonstrated that β-conglycinin could be the dietary source protein for the oligopeptides produced prior to entering the circulating bloodstream of rats.

DOI： 10.1016/j.foodchem.2020.128197

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It is unknown whether intestinal absorption of acylated anthocyanins occurs in their intact or metabolized form. In this study, with the aid of matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) ima- ging, intestinal absorption of acylated anthocyanins was visually investigated. Anthocyanin extracts from purple carrots were orally administered to Sprague-Dawley rats. Acylated cyanidins were absorbed into portal and circulating blood systems in their intact form, and aglycon; cyanidin 3-O-(6-O-feruloyl-β-D-glucopyranosyl)- (1 → 6)-[β-D-xylopyranosyl-(1 → 2)]-β-D-galactopyranoside (Cy3XFGG), and showed a high absorption of 39.3 ± 0.1 pmol/mL-plasma at 60 min after administration. MALDI-MS imaging analysis of the rat jejunum membranes showed that an organic anion transporting polypeptide (OATP) transporter was involved in Cy3XFGG transport, while deacylated anthocyanins were incorporated through both the glucose transporter 2 and OATP routes. In conclusion, acylated anthocyanin, Cy3XFGG, can be absorbed in its intact form through intestinal OATP.

DOI： 10.1016/j.foodchem.2020.127586

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The study investigated the effects of theaflavins, which are intestinally non-absorbable compounds, on intestinal
glucose transport in Caco-2 cells. 13C6-Glucose transport experiments clearly revealed that glucose transport
across Caco-2 cells was significantly (p < 0.01) inhibited by theaflavins. When Caco-2 cells were treated with 40
μM theaflavins for 24 h, the expression of SGLT1 expression was significantly (p < 0.05) suppressed, whereas no
difference in GLUT2 expression was observed. The theaflavin-induced inhibition of glucose transport was
reversed by the inhibition of influx routes mediated by OATP and MCT transporters. A Wes analysis established
that theaflavin-induced phosphorylation of AMPK was significantly (p < 0.05) suppressed by the inhibition of 2+
endoplasmic reticulum Ca -release and CaMKK β. These findings demonstrated for the first time that theaflavins can inhibit glucose transport across Caco-2 cell monolayers through the suppression of SGLT1 expression partly via the activation of the intracellular Ca2+/CaMKK β/AMPK signaling pathway.

DOI： https://doi.org/10.1016/j.jff.2020.104273

Repository Public URL： http://hdl.handle.net/2324/4772811

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The anti-hypertensive effects of hesperidin and hesperidin-containing fermented Mikan tea were investigated in 8-week-old spontaneously hypertensive rats (SHRs) at a dose of 50 mg/kg body weight for both, over 20 weeks. At the end of the protocol, a significant (P < 0.05) reduction in the systolic blood pressure (SBP) of approximately 60 mmHg was observed in the SHRs with the intake of hesperidin and Mikan tea. No change in the heart rate was observed between groups. Hesperidin altered the impaired vasomotor response in 28-week-old SHRs. Investigation of receptor expression related to mitogen-stimulated vasomotor action revealed that the Mas receptor (MasR) in the aorta of hesperidin-administered SHRs was up-regulated, while no changes in angiotensin II-type 1 and type 2 receptor expressions were observed. An increase in cAMP levels was confirmed in the aorta of hesperidin-administered SHRs, demonstrating that anti-hypertensive hesperidin plays a role in vessel regulation via the upregulated-MasR/cAMP axis.

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DOI： https://doi.org/10.1038/s41598-020-73464-8

Repository Public URL： http://hdl.handle.net/2324/4772824

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Language：English   Publishing type：Research paper (scientific journal)  

In this study, we were challenging to identify characteristic compounds in breast cancer cell lines. GC analysis of extracts from the culture media of breast cancer cell lines (MCF-7, SK-BR-3, and YMB-1) using a solid-phase Porapak Q extraction revealed that two compounds of moderate volatility, 1-hexadecanol and 5-(Z)-dodecenoic acid, were detected with markedly higher amount than those in the medium of fibroblast cell line (KMST-6). Furthermore, LC-TOF/MS analysis of the extracts clarified that in addition to the above two fatty acids, the amounts of five unsaturated fatty acids [decenoic acid (C10:1), decadienoic acid (C10:2), 5-(Z)-dodecenoic acid (C12:1), 5-(Z)-tetradecenoic acid (C14:1), and tetradecadienoic acid (C14:2)] in MCF-7 medium were higher than those in medium of KMST-6. Interestingly, H2O2-oxidation of 5-(Z)-dodecenoic acid and 5-(Z)-tetradecenoic acid produced volatile aldehydes that were reported as specific volatiles in breath from various cancer patients, such as heptanal, octanal, nonanal, decanal, 2-(E)-nonenal, and 2-(E)-octenal. Thus, we concluded that these identified compounds over-produced in breast cancer cells in this study could serve as potential precursors producing reported cancer-specific volatiles.

DOI： 10.1371/journal.pone.0235442

Repository Public URL： http://hdl.handle.net/2324/4772277

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DOI： 10.1021/acs.jafc.0c02475

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The physiological actions of orally ingested peptides on the brain remain poorly understood. This study examined the effects of 39 orally administered synthetic Tyr-containing dipeptides on the enhancement of brain norepinephrine metabolism in mice by comparing the concentration of 3-methoxy-4-hydroxyphenylethyleneglycol (MHPG). Although Tyr-Tyr administration increased blood and cerebral cortex (Cx) Tyr concentrations the most, Tyr-Trp increased Cx MHPG concentration the most. The oral administration of Tyr-Trp ameliorated a short-term memory deficit of a mouse model of cognitive dysfunction induced by amyloid beta peptide 25–35. Gene expression profiling of mouse brain using a microarray indicated that Tyr-Trp administration led to a wide variety of changes in mRNA levels, including the upregulation of genes encoding molecules involved in catecholamine metabolism. A comparative metabolome analysis of the Cx of mice given Tyr-Trp or Tyr-Tyr demonstrated that Tyr-Trp administration yielded higher concentrations of Trp and kynurenine pathway metabolites than Tyr-Tyr administration, as well as higher L-dopa levels, which is the initial product of catecholamine metabolism. Catecholamines were not significantly increased in the Cx of the Tyr-Tyr group compared with the Tyr-Trp group, despite a marked increase in Tyr. Presumably, Tyr-Trp administration enhances catecholamine synthesis and metabolism via the upregulation of genes involved in Tyr and Trp metabolism as well as metabolites of Tyr and Trp. These findings strongly suggest that orally ingested Tyr-Trp modulates the brain metabolome involved in catecholamine metabolism and contributes to higher brain function.

DOI： 10.1371/journal.pone.0232233

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In this study, experiments on amyloid β peptide_25-35-induced mice were performed to provide in vivo evidence on the potential of the blood–brain barrier transportable soy dipeptide, Tyr-Pro, in combating memory impairment. We demonstrated for the first time that oral administration of Tyr-Pro (100 mg/kg, twice a day) in mice for 16 days significantly improved impaired memory by spontaneous alternation and shortened step-through latency in amyloid β-induced mice.

DOI： 10.1038/s41538-020-0067-3

Repository Public URL： http://hdl.handle.net/2324/4772283

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Objectives We developed a fermented tea made by mixing thinned satsuma Mandarin fruit and green tea leaves at the level of 1 =3. This fermented tea contained hesperidin which has the high water-soluble property. We investigated the effects of feeding hesperidin derived from fer-mented tea leaves for 12 weeks on blood pressure in volunteers. Methods Thirty nine Subjects with high-normal blood pressure and stage I hypertension participated in a randomized, double-blind, placebo-controlled, parallel-group comparative test. Subjects consumed test beverage containing 1.20g fermented tea leaves or placebo beverAâge without tea leaves for 12 weeks. Systolic and diastolic blood pressures were measured every 4 weeks. Results Beverage containing fermented tea leaves reduced systolic blood pressures after the start of feeding. Also, systolic blood pressures were significantly lower in the test beverage group than in the placebo beverage group during feeding period. Conclusions The results suggested that feeding hesperidin derived from fermented lea leaves made by mixing thinned satsuma Mandarin fruit and tea leaves has an effect decreasing systolic blood pressures in subjects with high-nomial blood pressure and stage I hypertension.

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Matrix-assisted laser desorption/ionisation mass spectrometry imaging (MALDI-MSI) is presently used in physiological evaluations for visualisation of targets in organs. In the present study, MALDI-MSI was used as a visualisation technique to investigate the intestinal absorption of polyphenols. Nifedipine/phytic acid-aided MALDI-MSI was performed to visualise theaflavin-3′-O-gallate (TF3′G) and epicatechin-3-O-gallate (ECG) in the rat jejunum for 50-µM, 60-min transport experiments. Non-absorbable TF3′G was successfully visualised at the apical region, whereas absorbable ECG was detected throughout the rat jejunum. MALDI-MSI was also performed to determine the transport routes of the target metabolites. Signals corresponding to TF3′G and ECG in the membranes were diminished following treatment with inhibitors targeting the monocarboxylic acid transporter and organic anion transporting polypeptides. Enhanced visualisation of TF3′G was achieved by inhibiting efflux routes. Our findings demonstrated that the present MALDI-MSI can provide critical spatial informations on intestinal absorption of targets, by which TF3′G and ECG were incorporated into intestinal tissues, followed by efflux back to the apical compartment. In addition, MALDI-MSI analyses suggested that TF3′G was resistant to phase II metabolism during the influx/efflux processes, whereas ECG was susceptible to methylation and sulphation reactions. In conclusion, inhibitor-aided MALDI-MSI could serve as a powerful in situ visualisation technique for verifying intestinal transport routes and investigating the metabolism of penetrants.

DOI： 10.1038/s41598-019-39405-w

Repository Public URL： http://hdl.handle.net/2324/4772823

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Apart from nutrients required for the brain, there has been no report that naturally occurring peptides can cross the blood-brain barrier (BBB). The aim of this study was to identify the BBB-transportable peptides using in situ mouse perfusion experiments. Based on the structural features of Gly-N-methylated Gly (Gly-Sar), a reported BBB-transportable compound, 18 dipeptides were synthesized, and were perfused in the mouse brain for two minutes. Among the synthesized dipeptides, Gly-Sar, Gly-Pro, and Tyr-Pro were transported across the BBB with K
_i
values of 7.60 ± 1.29, 3.49 ± 0.66, and 3.53 ± 0.74 µL/g·min, respectively, and accumulated in the mouse brain parenchyma. Additionally, using MALDI-MS/MS imaging analysis of Tyr-Pro-perfused brain, we provide evidence for Tyr-Pro accumulation in the hippocampus, hypothalamus, striatum, cerebral cortex, and cerebellum of mouse brain.

DOI： 10.1038/s41598-019-42099-9

Language：English   Publishing type：Research paper (scientific journal)  

We investigated the absorption and metabolic behavior of hesperidin (hesperetin-7-O-rutinoside) in the blood system of Sprague-Dawley rats by liquid chromatography- and matrix-assisted laser desorption ionization mass spectrometries (LC-MS and MALDI-MS). After a single oral administration of hesperidin (10 mg/kg), which was expected to be absorbed in its degraded hesperetin form, we detected intact hesperidin in the portal vein blood (t_max, 2 h) for the first time. We successfully detected glucuronized hesperidin in the circulating bloodstream, while intact hesperidin had disappeared. Further MS analyses revealed that homoeriodictyol and eriodictyol conjugates were detected in both portal and circulating blood systems. This indicated that hesperidin and/or hesperetin are susceptible to methylation and demethylation during the intestinal membrane transport process. Sulfated and glucuronized metabolites were also detected in both blood systems. In conclusion, hesperidin can enter into the circulating bloodstream in its conjugated forms, together with the conjugated forms of hesperetin, homoeriodictyol, and/or eriodictyol.

DOI： 10.1021/acs.jafc.9b03594

Language：English   Publishing type：Research paper (scientific journal)  

In this study, a simultaneous assay for catecholamines and their metabolites in the brain was established using liquid chromatography-mass spectrometry (LC-MS). To achieve complete separation, a cation-exchange/reversed-phase mixedmode copolymer resin column containing 0.81 wt% sulfo groups was used for the simultaneous LC-MS assay. The analyzed catecholamines were dopamine (DA), norepinephrine (NE), and epinephrine (E), while the metabolites lacking amino groups were 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), and 3-methoxy-4- hydroxyphenylglycol (MHPG). The metabolites were separated and detected using LC-MS, on columns with and without sulfo groups. However, we could not achieve adequate separation of catecholamines on both columns using a gradient elution of 0 - 50 (v/v)% methanol containing 0.1 (v/v)% formic acid (FA). When volatile ion-pairing reagents were added to the mobile phase, they improved the retention and detection of catecholamines on the sulfonated mixed-mode column. Under optimized elution conditions, which involved a linear gradient elution of water containing 0.1 (v/v)% FA to 50 (v/v)% acetonitrile in 50 mM ammonium formate at 40°C and a 0.20 mL/min rate, all six target molecules were simultaneously detected within 25 min, when using negative mode LC-MS on a sulfonated mixed-mode column. The limits of detection (LODs) for DA, NE, E, DOPCA, HVA, and MHPG were determined to be 20.7, 12.6, 74.6, 1110, 18.7, and 3196 nM, respectively. Moreover, the established LC-MS assay allowed the detection of endogenous DA, NE, and HVA, in normal mouse brain samples at concentrations higher than 20, 9, and 4 pmol/mg, respectively.

DOI： 10.2116/analsci.18P494

Language：Japanese   Publishing type：Research paper (scientific journal)  

Anti-diabetic Effect of Acetic Acid-Free Red Vinegar in Spontaneously Diabetic Torii Rats

DOI： 10.3136/nskkk.65.552

Language：English   Publishing type：Research paper (scientific journal)  

Long-term estrogen deprivation (LTED) of an estrogen receptor (ER) α-positive breast cancer cell line recapitulates cancer cells that have acquired estrogen-independent cell proliferation and endocrine therapy resistance. Previously, we have shown that a cluster of non-coding RNAs, Eleanors (ESR1 locus enhancing and activating non-coding RNAs) formed RNA cloud and upregulated the ESR1 gene in the nuclei of LTED cells. Eleanors were inhibited by resveratrol through ER. Here we prepared another polyphenol, glyceollin I from stressed soybeans, and identified it as a major inhibitor of the Eleanor RNA cloud and ESR1 mRNA transcription. The inhibition was independent of ER, unlike one by resveratrol. This was consistent with a distinct tertiary structure of glyceollin I for ER binding. Glyceollin I preferentially inhibited the growth of LTED cells and induced apoptosis. Our results suggest that glyceollin I has a novel role in LTED cell inhibition through Eleanors. In other words, LTED cells or endocrine therapy-resistant breast cancer cells may be ready for apoptosis, which can be triggered with polyphenols both in ER-dependent and ER-independent manners.

DOI： 10.1038/s41598-018-33227-y

Language：English   Publishing type：Research paper (scientific journal)  

Brain-derived neurotrophic factor (BDNF), a member of the neurotrophin family, plays an important role in cognitive abilities, including memory and learning. We demonstrated that soybean protein hydrolysate (SPH) diet suppresses age-related cognitive decline via the upregulation of BDNF in a mouse model of senescence. Our purpose was to identify novel bioactive peptides in SPH, which enhance BDNF expression. We treated mouse primary astrocytes with SPH as well as with its positively charged chromatographic fraction. Significant increases in the expression of BDNF were observed in the treatment with positively charged fraction of SPH. Among the synthesized peptides, the dipeptide glycine-arginine (GR) increased BDNF expression in vitro, and LC-TOF-MS analysis showed the presence of GR in the SPH. Furthermore, its administration in vivo increased the expression of BDNF in the cerebral cortex and the number of neurons in hippocampus and cerebral cortex. These data indicate that GR might promote neurogenesis by upregulating BDNF levels.

DOI： 10.1021/acs.jafc.8b01581

Language：English   Publishing type：Research paper (scientific journal)  

The aim of this study was to develop an analytical method for the discrimination of reducing and non-reducing monosaccharides including rare sugars on a prototype hydrophilic interaction liquid chromatography (HILIC) column. The HILIC column was composed of a glycidyl methacrylate-ethylene glycol dimethacrylate copolymer attached to 8 wt% polyethyleneimine. Seven monosaccharides (reducing aldoses: D-xylose, D-allose, and D-glucose; non-reducing ketoses: D-fructose, D-psicose, D-sorbose, and D-tagatose) were targeted. In individual HPLC analysis of both aldoses and ketoses, elution with 90 v/v% acetonitrile permitted successful detection and separation only for the non-reducing ketoses. Besides, elution of a mixture of ketoses and aldoses with 85 v/v% acetonitrile containing 5 mmol/L sodium 1-octanesulfonate (OS) (pH 4.8) enabled the simultaneous separation of all seven monosaccharides within 40 min. The polyethyleneimine-attached HILIC column allowed discriminant HPLC analysis for non-reducing ketoses using elution with 90 v/v% acetonitrile, whereas elution with 85 v/v% acetonitrile containing 5 mmol/L OS simultaneously detected both ketoses and aldoses.

DOI： 10.3136/fstr.24.501

Language：English   Publishing type：Research paper (scientific journal)  

The beneficial health effects of edible sea urchin consumption in mice fed a normal (ND) or high-fat diet (HFD) were investigated in this study. Notably, sea urchin-administered (250, 500, 1000 mg/kg) mice exhibited lower body, liver, and visceral fat weights, lower plasma levels of aspartate aminotransferase and alanine aminotransferase, and lower hepatic triacylglycerol levels than those fed carboxymethyl cellulose (CMC). Despite the high levels of cholesterol found in sea urchins, intake of these organisms had no effect on plasma cholesterol levels among the mice tested. Additionally, sea urchin consumption resulted in enhanced levels of arachidonic acid and docosahexaenoic acid within mouse livers. Lastly, mice fed HFD with sea urchin (500 mg/kg) exhibited increased mRNA expression of uncoupling protein-1 within brown adipose tissue, compared with those fed HFD with CMC. In conclusion, consumption of sea urchin might provide a protective effect against the development of obesity and/or nonalcoholic fatty liver disease.

DOI： 10.1016/j.jff.2018.04.063

Language：English   Publishing type：Research paper (scientific journal)  

We investigated whether tomatoside A (5α-furostane-3β,22,26-triol-3-[O-β-d-glucopyranosyl (1→2)-β-d-glucopyranosyl (1→4)-β-d-galactopyranoside] 26-O-β-d-glucopyranoside), a tomato seed saponin, may play a role in the regulation of intestinal glucose transport in human intestinal Caco-2 cells. Tomatoside A could not penetrate through Caco-2 cell monolayers, as observed in the transport experiments using liquid chromatography-mass spectrometry. The treatment of cells with 10 μM tomatoside A for 3 h resulted in a 46.0% reduction in glucose transport as compared to untreated cells. Western blotting analyses revealed that tomatoside A significantly (p < 0.05) suppressed the expression of glucose transporter 2 (GLUT2) in Caco-2 cells, while no change in the expression of sodium-dependent glucose transporter 1 was observed. In glucose transport experiments, the reduced glucose transport by tomatoside A was ameliorated by a protein kinase C (PKC) inhibitor and a multidrug resistance-associated protein 2 (MRP2) inhibitor. The tomatoside A-induced reduction in glucose transport was restored in cells treated with apical sodium-dependent bile acid transporter (ASBT) siRNA or an ASBT antagonist. These findings demonstrated for the first time that the nontransportable tomato seed steroidal saponin, tomatoside A, suppressed GLUT2 expression via PKC signaling pathway during the ASBT-influx/MRP2-efflux process in Caco-2 cells.

DOI： 10.1021/acs.jafc.7b06078

Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: Prediabetes, a high-risk state for developing diabetes showing impaired glucose tolerance but a normal fasting blood glucose level, has an increasing prevalence worldwide. However, no study investigating the prevention of impaired glucose tolerance at the prediabetic stage by anti-diabetic functional foods has been reported. Thus, the present study aimed to evaluate the anti-prediabetic effect of rose hip in a prediabetic rat model. RESULTS: Spontaneously diabetic Torii (SDT) rats were supplemented with hot-water extract of rose hip at a dose of 100 mg kg^–1 body weight day^–1 for 12 weeks. The results obtained showed that the supplementation of rose hip extract improved impaired glucose tolerance, promoted insulin secretion, preserved pancreatic beta-cell function and suppressed plasma advanced glycation end-products formation of methylglyoxal-derived hydroimidazolone (MG-H1) residue and N^ϵ-carboxymethyl-lysine residues (e.g. MG-H1, control: 465.5 ± 43.8 versus rose hip: 59.1 ± 13.0 pmol mg protein^–1, P < 0.05) in SDT rats at the prediabetic stage (12–20 weeks old). CONCLUSION: The present study provides the first evidence showing that a hot-water extract of rose hip could exert an anti-prediabetic effect in a rat model.

DOI： 10.1002/jsfa.8254

Language：English   Publishing type：Research paper (scientific journal)  

In the present study, we aimed to evaluate the effect of aging on the absorption of small peptides in spontaneously hypertensive rats (SHRs). Three kinds of dipeptides, glycyl-sarcosine (Gly-Sar), Trp-His, and captopril (a dipeptidomimetic drug), a Gly-Sar-Sar tripeptide, a Gly-Sar-Sar-Sar tetrapeptide, and a Gly-Sar-Sar-Sar-Sar pentapeptide were administered at doses of 10 mg/kg each to 8- and 40-week-old SHRs. The peptides were all detected in their intact forms in the blood. There was a significantly promoted absorption of di/tripeptides in aged SHRs compared with young SHRs. In contrast, the absorption of tetra/pentapeptides was not affected by aging. PepT1 expression in the mid-jejunum was significantly increased in 40-week-old SHRs compared with 8-week-old SHRs, whereas aging did not alter the expression of claudin-1, a tight junction related protein. Thus, the present results suggest that SHR aging may enhance the absorption of di/tripeptides through the enhanced PepT1 transport route, although oligopeptides may be absorbed in an age-independent manner.

DOI： 10.1021/acs.jafc.7b01727

Language：English   Publishing type：Research paper (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.foodchem.2016.06.059

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1002/jms.3805

Repository Public URL： https://hdl.handle.net/2324/7169328

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1007/s00210-016-1264-0

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1080/09168451.2016.1214530

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1021/acs.jafc.6b00665

Language：English   Publishing type：Research paper (scientific journal)  

重合カテキンであるテアシネンシンAが苦みペプチドである各種のトリプトファン含有ジペプチドの苦み応答を抑制し、かつ園現象は溶液内での両者の複合体形成であることをin vitroおよびin silico解析によって突き止めたこと。

DOI： 10.1371/journal.pone.0157315

Language：English   Publishing type：Research paper (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)  

Our study is the first to demonstrate the vasorelaxant effect of Candida utilis yeast extract on rat aorta (EC₅₀ of 7.2 ± 3.2 mg/mL). Among five identified compounds, 5′-methylthioadenosine (MTA) exhibited comparable vasorelaxant effect (EC₅₀ of 190 ± 40 μM) with adenosine, a known vasodilator, on 1 μM phenylephrine (PE)-contracted Sprague-Dawley rat aortic rings. MTA induced vasorelaxation in an endothelium-independent manner and independent of the adenosine receptors. MTA reduced a CaCl2-induced vasocontraction stimulated by 1 μM PE, whereas the effect was abolished in a 60 mM KCl-induced vasocontraction. This indicates that MTA was not involved in the suppression of extracellular Ca²⁺ influx. MTA significantly (P < 0.01) attenuated the PE-induced activation of calmodulin-dependent kinase II (CaMK II) in aortic rings and inhibited the phosphorylation of L-type Ca²⁺ channel (VDCC). In conclusion, the underlying mechanism(s) of MTA-induced vasorelaxation involves the inhibition of Ca²⁺/CaMK II/VDCC phosphorylation pathway, resulting in the suppression of intracellular Ca²⁺ concentration in aortic rings.

DOI： 10.1021/acs.jafc.6b00679

Repository Public URL： https://hdl.handle.net/2324/7168679

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1021/acs.jafc.6b00279

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.foodchem.2015.05.053

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.lfs.2015.12.044

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.3136/fstr.22.127

Language：English   Publishing type：Research paper (scientific journal)  

The aim of this study was to visualize the sorption of tocopherol acetate as a penetrant into polymer films. A matrix-assisted laser desorption/ionization-imaging mass spectrometry (MALDI-IMS) technique was used to visualize the distribution of tocopherol acetate in films during the migration process. A phytic acid-aided MALDIIMS using 2',4',6'-trihydroxyacetophenone as a matrix allowed us to successfully visualize the absorbed tocopherol acetate in both ethylene-vinyl acetate copolymer (EVA) and low-density polyethylene (LDPE) films after 1 weekstorage of tocopherol acetate at 40°C. The IMS technique allowed us to also visualize the actual distribution of tocopherol acetate inside the EVA/barrier/EVA laminated films, in which tocopherol acetate sorption was blocked at the barrier layer.

DOI： 10.3136/fstr.21.821

Repository Public URL： https://hdl.handle.net/2324/7169335

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1007/s00210-015-1171-9

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1080/09168451.2015.1044932

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1002/mnfr.201500075

Language：English   Publishing type：Research paper (scientific journal)  

Prediabetes, typically defined as impaired glucose tolerance and/or impaired fasting blood glucose, is a high-risk state of developing diabetes. The association of diabetes-related metabolites with prediabetes has not been investigated intensively. This study aimed to get insights into the metabolic behaviors of some typical diabetes-related metabolites in plasma of male Spontaneously Diabetic Torii (SDT) rats during pathogenic progress of diabetes and to assess in vivo if the variation in these metabolites related to the progression of prediabetic stage. To address this question, SDT rats and Sprague Dawley (SD) rats as control were maintained from the age of 7 to 25 weeks. Five typical advanced glycation end products (AGEs) residue of plasma protein and their free adducts were determined by liquid chromatography with tandem mass detection over the duration of the investigation. The SDT rats exhibited impaired glucose tolerance since the age of 12 weeks and developed diabetes with significantly elevated fasting glucose levels after 22 weeks. At the prediabetic stage (12–21 weeks), no significant differences were observed on AGEfree adducts levels of SDT rats compared with SD rats. However, methylglyoxal- derived hydroimidazolone (MG-H1) residue contents of plasma protein were significantly elevated in SDT rats at the age of 16 weeks, whereas other AGE residues of plasma protein did not show marked difference. The present study has revealed significant increase in MG-H1 residue content of plasma protein at the prediabetic stage of a spontaneously diabetic rat model, irrespective of unaltered fasting blood glucose and constant plasma levels of other AGEs.

DOI： 10.14814/phy2.12477

Repository Public URL： https://hdl.handle.net/2324/7169333

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1007/s11095-015-1621-6

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.foodchem.2014.08.105

Language：English   Publishing type：Research paper (scientific journal)  

The purpose of this study was to gain insight into the production behavior of free adducts of advanced glycation end-products (AGEs) in Wistar rats under acute hyperglycemic conditions. Five AGE-free adducts as well as their precursors (i.e., highly reactive carbonyl intermediates of methylglyoxal and glyoxal) in rat plasma were quantitatively determined at greater than nanomolar levels using the liquid chromatography/ tandem mass spectrometry method coupled with 2,4,6-trinitrobenzene sulfonate and 2,3-diaminonaphthalene derivatization techniques. An oral glucose (2 g/kg dose) tolerance test to 10-week-old Wistar rats provided evidence that the plasma levels of diabetes-related metabolites did not change acutely within 120 min, irrespective of increasing blood glucose levels.

DOI： 10.1248/bpb.b14-00698

Repository Public URL： https://hdl.handle.net/2324/7169332

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1080/09168451.2014.951027

Language：English   Publishing type：Research paper (scientific journal)  

Repository Public URL： https://hdl.handle.net/2324/7168376

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.bbagen.2014.07.020

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1021/jf503257w

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.jnutbio.2014.03.013

Language：English   Publishing type：Research paper (scientific journal)  

Repository Public URL： https://hdl.handle.net/2324/7168377

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.foodchem.2013.11.143

Language：English   Publishing type：Research paper (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1371/journal.pone.0088975

Language：Japanese   Publishing type：Research paper (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.bcp.2013.10.029

Language：English   Publishing type：Research paper (scientific journal)  

Repository Public URL： https://hdl.handle.net/2324/7167113

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.foodchem.2012.12.026

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.foodchem.2012.10.137

Language：English   Publishing type：Research paper (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)  

生体内での糖化産物である各種AGEを高感度分析する新たなアッセイ法（LC-MS/MS-MRM-TNBS法）を提案した。

DOI： 10.1021/ac400294q

Repository Public URL： https://hdl.handle.net/2324/7168688

Language：English   Publishing type：Research paper (scientific journal)  

Repository Public URL： https://hdl.handle.net/2324/7168660

Language：English   Publishing type：Research paper (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.ejphar.2012.07.011

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.fob.2012.04.005

Language：English   Publishing type：Research paper (scientific journal)  

Adenine had a concentration-dependent relaxation action on the phenylephrine-contracted aorta ring, with an EC₅₀ value of 0:40 ± 0:12mM. This effect was also observed in the endothelium-denuded aorta. Among the adenine analogues, N-methyladenine and benzimidazole still evoked an apparent relaxation effect, while 1-, 3- or 7-methyladenine and imidazole were no longer vasodilators. These findings demonstrate that the imino group from the uncharged imidazolium moiety in adenine played a key role in the relaxation of the contracted aorta.

DOI： 10.1271/bbb.110806

Repository Public URL： https://hdl.handle.net/2324/7168380

Language：English   Publishing type：Research paper (scientific journal)  

Repository Public URL： https://hdl.handle.net/2324/7168676

Language：English   Publishing type：Research paper (scientific journal)  

The sorption behavior of a fluorescent reagent into a polymer film was visualized by confocal laser scanning microscopy (CLSM), and the effects of the additives, film types, and film depth on the diffusion coefficient (D) of the fluorescence reagent were examined. Perylene and cellulose acetate (CA) were used as a fluorescent reagent and a polymer material, respectively. Perylene dissolved in the additives triethylene glycol diacetate (TEGDA) and glycerol triacetate (GTA) was added to the CA film. Then, the evaluation of two types of CA films, a closed-system cellulose acetate (CCA) sample and an open-system cellulose acetate (OCA) sample, was conducted. At optimized CLSM conditions (with a scanning range at a 20-lm depth from the CA film surface with 1-μm intervals and a scanning speed of 1 fps), the sorption of perylene at the inner CA film was determined. The D values of perylene in the CA film were calculated pursuant to Fick's second law. Higher D values of perylene mixed with TEGDA versus those of perylene mixed with GTA were commonly obtained for the CCA sample (TEGDA: 8.9 × 10^-15 m ^2/s > GTA: 1.7 × 10^-15 m^2/s) and the OCA sample (TEGDA: 11 × 10^-15 m^2/s > GTA: 3.3 × 10^-15 m ^2/s) because of the higher chemical affinity of TEGDA with perylene than that of GTA. Perylene indicated a higher D value and was homogeneously distributed in the case of the OCA sample; we found that diffusivity and distribution of perylene in CA film were largely affected by the multistratification treatment. We also proved that the deeper the film depth was, the lower the diffusivity of perylene was, regardless of the types of additives and films. The factors considered for the film-depth dependence of D were a gradual increase in the diffusion pathway for perylene caused by additive diffusion and the concentration dependence of the perylene D.

DOI： 10.1002/app.33322

Repository Public URL： https://hdl.handle.net/2324/7168365

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.ab.2011.02.037

Language：English   Publishing type：Research paper (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)  

The candidates responsible for vasorelaxation action of rutin-free tartary buckwheat extract (TBSP) were examined in this study. As a result of reversed-phase high-performance liquid chromatography (HPLC) separations, five prominent peaks in the acidic fraction of TBSP were obtained at 260 nm. Among the five collected peaks, we successfully identified four compounds by nuclear magnetic resonance (NMR) and mass spectrometry (MS) measurements: (+)-osbeckic acid as a dimer ([M - H]- m/z: 371.2 > 184.9 > 140.9), 5-hydroxymethyl-2-furoic acid, protocatechuic acid, and p-hydroxybenzoic acid. A vascular contractive measurement in 1.0 μM phenylephrine-contracted Sprague-Dawley rat thoracic aorta rings revealed that (+)-osbeckic acid dimer evoked a potent vasorelaxant effect with an EC₅₀ value of 887 μM compared to other isolates (EC50: 5-hydroxymethyl-2-furoic acid, 3610 μM; protocatechuic acid, 2160 μM; p-hydroxybenzoic acid, no inhibition). Dimeric (+)-osbeckic acid was stable in solutions and at high temperatures, while its degraded peak on the HPLC chromatogram was observed when it was dissolved in dimethyl sulfoxide.

DOI： 10.1021/jf1028416

Repository Public URL： https://hdl.handle.net/2324/7168677

Language：English   Publishing type：Research paper (scientific journal)  

Background: A new fermented tea produced by tea-rolling processing of loquat (Eriobotrya japonica) leaf with green tea leaf (denoted as LG tea) showed a potent antihyperglycaemic effect in maltose-loaded rats. The aim of this study, therefore, was to identify α-glucosidase inhibitors in the antihyperglycaemic tea product. Results: LG tea had a threefold higher maltase-inhibitory activity (IC₅₀ 0.065 mgdried extractm L_-1) than either the constituent loquat leaf or green tea alone. In addition, LG tea favourably inhibited maltase action rather than sucrase action. As a result of bioguided high-performance liquid chromatography separations of LG tea, theasinensin A, theasinensin B, strictinin and 1,6-digalloylglucose were newly identified asmaltase inhibitors with IC50 values of 142, 225, 398 and 337 μmol L^-1 respectively, along with previously identified catechins and theaflavins. Conclusion: Judging from the magnitude of the α-glucosidase-inhibitory contribution of each isolated compound to the overall inhibition of LG tea, catechins were the main candidates responsible for α-glucosidase or maltase inhibition in LG tea, followed by theaflavins, theasinensins, strictinin and 1,6-digalloylglucose.

DOI： 10.1002/jsfa.3983

Repository Public URL： https://hdl.handle.net/2324/7168682

Language：English   Publishing type：Research paper (scientific journal)  

In this study, we focused on the antihypertensive effect of newly fermented salt-free soy sauce (SFS) in spontaneously hypertensive rats (SHRs). A 13-wk oral administration of SFS was performed daily in 8- to 21-wk-old SHRs with a dose of 200 mg/kg of body weight/d. The systolic (SBP) and diastolic (DBP) blood pressures were measured for each week during the experimental period. As a result, a significant (P < 0.01) BP lowering effect was observed from the 5th d to the end of the experiment in the SFS group compared with the control group (ΔSBP_21-wk: 27 mmHg, ΔDBP_21-wk: 20 mmHg). In contrast to such substantial effect by SFS intake, angiotensin I-converting enzyme activities in blood and local organs as well as pharmaceutical parameters such as serum Na⁺ or K⁺ level did not show any significant difference between in both SFS and control groups. Vasoconstriction experiment using thoracic aorta rings from 21-wk SHRs provided an interesting result that the rings from the SFS group evoked a >2-fold higher increase in the angiotensin II-stimulated constrictive response compared with the rings from the control group (P = 0.012), which suggested that the SFS-intake would be effective in possessing a higher vessel tone.Practical Application: In this study, we investigated the antihypertensive effect of newly fermented SFS in SHRs. As a result of 13-wk SFS-administration, we found a significant antihypertensive effect of the SFS. This finding strongly demonstrates that the developed SFS would be greatly beneficial for health and useful for health-related industries.

DOI： 10.1111/j.1750-3841.2010.01599.x

Repository Public URL： https://hdl.handle.net/2324/7168681

Language：English   Publishing type：Research paper (scientific journal)  

The sorption behavior of a fluorescent reagent into a polymer film was visualized by confocal laser scanning microscope (CLSM), and the effect of additives on the sorption was examined. Perylene and cellulose acetate (CA) were used as a fluorescent reagent and a polymer material, respectively. Perylene dissolved in additives of glyc-erol triacetate (GTA), triethylene glycol diacetate (TEGDA), 1,3-butylene glycol diacetate (BGDA), paraffin liquid, and poly(ethylene glycol) 200 (PEG) were added onto CA film. At optimized CLSM conditions (scanning range of a 10 lm-depth from the CA film surface with 1 lm intervals and a scanning speed of 1 fps), the sorption of perylene at the inner CA film was determined. Diffusion coefficients of perylene in the CA film were calculated according to Fick's second law. When perylene was dissolved in TEGDA, the highest diffusion coefficient, 8.9 × 10^-15 m ²/s, among the additives was obtained because of high affinity of TEGDA with perylene, whereas the lowest diffusion coefficient was observed in paraffin liquid, which showed a low affinity with perylene. The diffusion coefficients of perylene in GTA, BGDA, and PEG also revealed that physical parameters, such as molecular size and viscosity, of the additives were additional factors affecting the perylene diffusivity in the CA film.

DOI： 10.1002/app.31607

Repository Public URL： https://hdl.handle.net/2324/7168364

Language：English   Publishing type：Research paper (scientific journal)  

Additives distributed in a polymer film were visualized by a confocal laser scanning microscope (CLSM) in this study. Cellulose acetate (CA) was used as the polymer film material. Perylene as a fluorescence reagent and glycerol triacetate (GTA) as a plasticizer for CA, respectively, were selected and mixed for visualizing the absorption of perylene into CA. Under optimized CLSM conditions of an objective lens (dry, 20×) and diode laser (408 nm, 290-330 μW), a fluorescent penetrant, perylene, in GTA solution was detected in CA casting film within around 9 μm depth of the film in 60 minutes after starting the sorption study. It was also found that the fluorescence intensity of perylene became lower with the film depth. This finding suggested that CLSM could visualize the sorption behavior of perylene as a dynamic diffusion process. Analytical conditions, such as a scanning range along the Z axis (±10 or ±30 μm from an air-contact surface of the CA film) and a scan speed (1 or 30 fps) of CLSM, did not affect the fluorescence intensity of the sorbed perylene. It was concluded that a newly developed analytical methodology using CLSM was sufficient for visualizing the perylene penetrant across the cross-sectional distribution of the CA film, being capable of monitoring the sorption behavior of compounds in polymer materials without any destruction of a given absorbed film.

DOI： 10.1002/app.31392

Repository Public URL： https://hdl.handle.net/2324/7168363

Language：English   Publishing type：Research paper (scientific journal)  

GC-MS analysis based on purge and trap sampling followed by Curie point thermal desorption was examined for the quantitative determination of 2,4,6-trichloroanisole in aqueous solutions. The method developed showed linearity in single ion monitoring mode over a TCA concentration range of 0.12-120 ng L^-1 (parts-per-trillion).

DOI： 10.1365/s10337-009-1428-x

Repository Public URL： https://hdl.handle.net/2324/7168659

Language：English   Publishing type：Research paper (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)  

The new acylated polyphenols were isolated from a red-colored vinegar produced via fermentation with purple-fleshed sweet potato storage roots, and identified mainly by MS and NMR. The three acylated sophoroses were determined as 6-O-(E)-caffeoyl-(2-O-(6-O-acyl)-β-D-glucopyranosyl)-D-glucopyranoses, where acyl was (E)-caffeoyl, p-hydroxybenzoyl, and (E)-feruloyl, respectively. The four acylated anthocyanins were also determined as cyanidin 3-O-(6-O-(E)-caffeoyl-(2-O-(6-O-(E)-feruloyl)β-D-glucopyranosyl) -β-D-glucopyranoside), in addition to peonidin 3-O-(6-O-(E)-caffeoyl-(2-O- (6-O-acyl)D-glucopyranosyl)-β-D-glucopyranosides), where acyl was (E)-caffeoyl, p-hydroxybenzoyl, and (£)-feruloyl, respectively. The diacylated sophoroses showed higher antioxidant capacity than that of monoacylated analogue 6-caffeoylsophorose, so the multiacylation established to enhance their antioxidant capacity. Similarly, 5-deglucosylated anthocyanins also gave somewhat stronger antioxidation than corresponding sweet potato anthocyanins. In rat intestinal α-glucosidase inhibition study, the diacylated sophoroses preferably inhibited maltase rather than sucrase with an IC₅₀ value of <300 μM, indicating a potential role as antidiabetic phytochemicals. These acylated polyphenols in a red vinegar were expected to play important functional roles for health.

DOI： 10.1021/jf901809p

Repository Public URL： https://hdl.handle.net/2324/7168678

Language：English   Publishing type：Research paper (scientific journal)  

In the present study, we primarily attempted to identify di- and tri-peptides showing potent vasodilation in 1.0 μM phenylephrine-contracted thoracic aortas of Sprague-Dawley rats. Synthetic 15 Trp-His (WH) skeleton analogues were used for rat aorta ring's force measurements, since WH was found to be a vasoactive di-peptide so far. Among the synthesized peptides consisted of both His and Trp amino acid residues, His-Arg-Trp (HRW) was found to evoke the most potent vasodilation with an EC₅₀ value of 1.2 ± 0.08 mM in an endothelium-independent manner, while no effect was evoked by a mixture of individual amino acids. In addition to the structure of tri-peptides-activity relationship, chemically modified HRW analogues, i.e., 1- or 3-methyl-His-Arg-Trp and His-citrulline-Trp demonstrated the structural importance of tri-peptide to evoke the vasoactivity as following factors: (1) Neutral imidazole and indole groups from His and Trp residues at N- and C-terminals, respectively and (2) basic amino acids at the middle position. In mitogen (10 μM angiotensin II or 50 μM Bay K8644)-stimulated vascular smooth muscle cells, vasoactive HRW (100 μM) caused significant [Ca²⁺]_i reduction to an extent of >30%. Thus, our results suggest that HRW caused vasodilation action via an endothelium-independent mechanism which probably involves the suppression of extracellular Ca²⁺ influx through voltage-gated l-type Ca²⁺ channel.

DOI： 10.1016/j.peptides.2009.05.012

Repository Public URL： https://hdl.handle.net/2324/7167122

Language：English   Publishing type：Research paper (scientific journal)  

In a project to produce a new fermented tea product from non-used tea leaves harvested In the summer, we found that kneading tea leaves (Camellia sinensis) with fresh loquat leaves (Eriobotrya japonica) accelerated the enzymatic oxidation of tea catechins. The fermented tea obtained by tea-rolling processing of tea and loquat leaves had a strong, distinctive flavor and a plain aftertaste, which differed from usual black, green, and oolong teas. The phenolic constituents were similar to those of black tea. However, the concentrations of theaflavin 3-O-gallate, theaflavin 3,3′-di-O-gallate, and thearubigins were higher in the tea leaves kneaded with loquat leaves than in tea leaves kneaded without loquat leaves. The results from in vitro experiments suggested that acceleration of catechin oxidation was caused by the strong oxidation activity of loquat leaf enzymes and a coupled oxidation mechanism with caffeoyl quinic acids, which are the major phenolic constituents of loquat leaves.

DOI： 10.1021/jf900963p

Language：Japanese   Publishing type：Research paper (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)  

In present study, we aimed to identify angiotensin I-converting enzyme (ACE)-inhibitory peptides from a salt-free soy sauce (SFS), a newly developed antihypertensive seasoning obtained by Aspergillus oryzae fermentation of soybean in the absence of salt, which can be transported through caco-2 cell monolayers. Through an Ussing transport investigation of SFS across caco-2 cell monolayers, three di-peptides, Ala-Phe, Phe-Ile and Ile-Phe, were successfully identified from the SFS as transportable inhibitory peptides. Ala-Phe and Ile-Phe, but not Phe-Ile, exhibited ACE-inhibitory activity with IC₅₀ values of 165.3 μM and 65.8 μM, respectively. Kinetic studies revealed that Ile-Phe (Km: 3.1 mM, P_app: 2.4 × 10^-6 cm/s) exhibited greater affinity toward the transport compared with Ala-Phe (K_m: 48.1 mM, P_app: 1.4 × 10^-6 cm/s) and Phe-Ile (K_m: 12.7 mM, P_app: 1.4 × 10^-6 cm/s).

DOI： 10.1016/j.peptides.2007.11.006

Repository Public URL： https://hdl.handle.net/2324/7168684

Language：English   Publishing type：Research paper (scientific journal)  

To clarify the postprandial glucose suppression effect of flavonoids, the inhibitory effects of catechins and theaflavins against α-glucosidase (AGH) were examined in this study. It was initially demonstrated that theaflavins and catechins preferentially inhibited maltase rather than sucrase in an immobilized AGH inhibitory assay system. For the maltase inhibitory effects of theaflavins, the effects were observed in descending order of potency of theaflavin (TF)-3-O-gallate (Gal) > TF-3,3′-di-O-Gal > TF-3′-O-Gal > TF. This suggests that the AGH inhibition induced by theaflavins is closely associated with the presence of a free hydroxyl group at the 3′-position of TF as well as the esterification of TF with a mono-Gal group. In addition, the R-configuration at the 3′-position of TF-3-O-Gal showed a higher inhibitory activity than the S-configuration. As a result of a single oral administration of maltose (2 g/kg) in rats, a significant reduction in blood glucose level was observed at a dose of 10 mg/kg of TF-3-O-Gal, demonstrating for the first time that TF-3-O-Gal can suppress glucose production from maltose through inhibition of AGH in the gut.

DOI： 10.1021/jf0627672

Repository Public URL： https://hdl.handle.net/2324/6141

Language：Japanese   Publishing type：Research paper (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1291/hypres.28.545

Repository Public URL： https://hdl.handle.net/2324/7169325

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1248/bpb.27.1797

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1021/jf035330s

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1002/psc.568

Language：Others   Publishing type：Research paper (scientific journal)  

Language：Japanese   Publishing type：Research paper (scientific journal)  

Antihypertensive effect of food containing sardine peptides in high-normal hypertensives amd hypertensives.

Language：Japanese   Publishing type：Research paper (scientific journal)  

SOD-like activity of sardine muscle hydrolysate by alkaline protease.

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/S0006-291X(03)00929-X

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1046/j.1440-1681.2003.03824.x

Repository Public URL： https://hdl.handle.net/2324/7169324

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1021/jf026146u

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/S0003-2670(02)01539-8

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1021/jf025913m

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1248/bpb.25.1228

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1002/psc.387

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/S0955-2863(01)00198-X

Language：Japanese   Publishing type：Research paper (scientific journal)  

Depressor effect of sardine peptide-drink in mild hypertensives and normotensives.

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1046/j.1440-1681.2002.03628.x

Repository Public URL： https://hdl.handle.net/2324/7169011

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1021/jf001251u

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1021/jf0012502

Language：English   Publishing type：Research paper (scientific journal)  

The inhibitory effects of natural and synthetic inhibitors on the intestinal membrane-bound hydrolase, α-glucosidase (AGH), were evaluated by using an immobilized cyanogen bromide-activated Sepharose 4B support. Immobilized AGH (iAGH) inhibition study by synthetic inhibitors (acarbose and voglibose) revealed that the magnitude of inhibition differed from that in the free AGH (fAGH) study: IC₅₀ value of acarbose in iAGH-maltase assay system, 340 - 430 nM; fAGH, 11 nM. iAGH-maltase inhibition by both inhibitors was influenced by blocking reagents with different functional groups (COOH, OH, CH₃, and NH₂ groups). On the other hand, significant iAGH-sucrase inhibitory activity was observed only when using the negatively charged support induced by 0.1 M β-alanine. The K(m) values obtained in the iAGH assay system were similar to those from the fAGH method. With natural inhibitors, the iAGH-sucrase inhibitory activity of D-xylose, with in vivo glucose suppression, increased twice compared to that in fAGH. Green tea extract gave almost the same inhibition for both AGH assay systems.

Repository Public URL： https://hdl.handle.net/2324/7169331

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1021/jf991082h

Language：English   Publishing type：Research paper (scientific journal)  

Repository Public URL： https://hdl.handle.net/2324/7169331

Language：Japanese   Publishing type：Research paper (scientific journal)  

Deviation of desorption equation of flavors from plastic films by using compatibility theory.

Language：Japanese   Publishing type：Research paper (scientific journal)  

Antihypertensive effect of sardine peptides in mild hypertensives and high-normal hypertensives.

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1038/sj.jhh.1001065

Repository Public URL： https://hdl.handle.net/2324/7169327

Language：English   Publishing type：Research paper (scientific journal)  

We report here the antihypertensive effect of wheat germ (WG) hydrolysate and its dominant peptide, Ile-Val-Tyr (IVY), with potent angiotensin I-converting enzyme (ACE) inhibitory activity. The toxicity test of AG50W fraction purified from the WG hydrolysate and IVY in tidy mice revealed that 1 week median lethal concentrations of AG fraction and IVY were less than 100 and 10 mg/kg, respectively. As a result of an intravenous administration test of both inhibitors in spontaneously hypertensive rat (SHR), the mean arterial blood pressure (MAP) significantly decreased with the dose; the MAP reduction of 10.3 and 19.2 mmHg was observed at a dose of 50 mg/kg of AG fraction and 5 mg/kg of IVY, respectively. In addition to this behavior, the MAP gradually decreased after the 5 mg/kg of IVY injection (time to give a maximum reduction; 8 min), and the reduction was held for 20 min. By using rat and human plasma, IVY was found to be metabolized by the action of aminopeptidase in plasma to form a subsequent ACE inhibitor, Val- Tyr (VY). Thus, the intake of IVY as a physiologically functional food would serve in the lowering of blood pressure (BP) by the combined depressor effect of itself and its metabolite after the absorption.

Repository Public URL： https://hdl.handle.net/2324/7168379

Language：Japanese   Publishing type：Research paper (scientific journal)  

Antihypertensive effect of sardine peptides and Val-Tyr - antihypertensive effect of the peptides in spontaneously hypertensive rats-

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/S0378-4347(99)00128-0

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1002/(SICI)1099-1387(199907)5:7<289::AID-PSC196>3.0.CO;2-6

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1021/jf9810214

Language：English   Publishing type：Research paper (scientific journal)  

The plasma concentrations of angiotensin (Ang) I, Ang II, and their metabolites (Ang (3-8), (4-8), (5-8), and (3-4)) following in vitro ACE inhibitory activity were examined in young male normotensive (NT) (n = 7), and mild hypertensive (HT) volunteers in = 6). There were no differences in supine plasma levels of Ang I, Ang II, and Ang (5-8) between the NT and HT groups: Ang I, 304 ± 43 fmol/ml vs. 293 ± 15 fmol/ml; Ang II, 32 ± 6 fmol/ml vs. 43 ± 10 fmol/ml; Ang (5-8), 176 ± 22 fmol/ml vs. 133 ± 32 fmol/ml. In addition, there were no significant differences between groups in any of these Ang levels when measured after standing for 60 min. However, the HT group showed significantly reduced supine and upright plasma Ang (3-8) and Ang (3-4) levels as compared to the NT group. In particular, the supine plasma level of Ang (3-4) (71 ± 13 fmol/ml-plasma) in the HT group was significantly (1/3-fold) lower than that in the NT group (197 ± 35 fmol/ml-plasma). An inverse correlation between the plasma level of Ang (3-4) and the upright systolic blood pressure (r = -0.627, p < 0.02, n = 13) was observed, indicating that the metabolism of Ang (3-4) might have been associated with the change in blood pressure.

Repository Public URL： https://hdl.handle.net/2324/7169326

Language：English   Publishing type：Research paper (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1021/jf980788t

Language：Japanese   Publishing type：Research paper (scientific journal)  

Antihypertensive effect of sardine peptides in mild hypertensive subjects.

Language：English   Publishing type：Research paper (scientific journal)  

Repository Public URL： https://hdl.handle.net/2324/7168674

Language：English   Publishing type：Research paper (scientific journal)  

The sorption of flavor compounds into low-density polyethylene (LDPE) and ethylene-vinyl alcohol copolymer (EVOH) films was greatly influenced by ethanol concentration, and maximal sorptions were observed at 5-10% (v/v) ethanol for LDPE and 10-20% (v/v) ethanol for EVOH. The sorptions of ethyl hexanoate, octanal, and octanol into LDPE film were ∼1.7, 16.5, and 2.5 times higher than those in the 0% (v/v) ethanol solution, respectively (for EVOH film, the sorption increments of these compounds were ∼6.2, 3.5, and 4.1 times, respectively). To better understand this phenomenon, the solvent properties of ethanol solutions were investigated. The dielectric constants were roughly unchanged in the range 5-15% (v/v) ethanol. According to the results obtained by ¹H NMR measurement, in which the difference in proton chemical shift from water-d (HDO) and ethyl alcohol-d (EtOD) became maximum at 23% (v/v) ethanol solution, the structural change of water induced by the addition of ethanol would be great up to 23% (v/v) ethanol. These results accurately reflected the sorption behavior. Therefore, the specific sorption behavior of flavor compounds from an ethanol solution would be brought about by the heterogeneous water-ethanol structure.

DOI： 10.1021/jf950707i

Language：English   Publishing type：Research paper (scientific journal)  

A fluorometric determination method for angiotensins (ANG I, II, III) in human plasma was developed with 2,3-naphthalenedialdehyde (NDA). Human plasma (10 ml) ultrafiltered with a Molucut L (< M.W. 5000) was put directly on a reversed-phase column for HPLC with an UV detector. The fractions containing each angiotensin were derivatized with 0.1 mM NDA in the presence of cyanide for 60 min at ambient temperature. The derivatized angiotensin (NDA-ANG) was injected onto the HPLC system with a fluorometric detector. Excitation and emission wavelengths were set at 420 nm and 490 nm, respectively. The peak areas of NDA-ANG were linearly related with the amount of angiotensin applied, and were highly reproducible (3.5%, n=5). The concentrations of ANG I, II and III in plasma, calculated from the respective calibration curve, were 315.8 pg/ml, 19.2pg/ml and <1.3pg/ml, respectively. The concentration of ANG II obtained by this fluorometric method coincided with that (22.6 pg/ml) by radioimmunoassay.

DOI： 10.2116/bunsekikagaku.44.783

Language：English   Publishing type：Research paper (scientific journal)  

The ACE inhibitory activity of an alkaline protease hydrolyzate from sardine muscle did not change after being treated by gastrointestinal proteases (IC₅₀ = 0.082mg protein/ml). Eleven new ACE inhibitory peptides, constructed with 2 to 4 amino acid residues, were isolated from the hydrolyzate. The ACE inhibitory activity of each was mostly below 100 μM of IC₅₀ value; the maximal inhibitory activity was observed for Lys-Trp (IC₅₀ = 1.63 μM). The isolated peptides inhibited ACE competitively, except for Met-Tyr with non-competitive inhibition. As the result of sequence homology, Arg-Val-Tyr isolated from the hydrolyzate was found in the primary structure of angiotensins I, II, and III, and of des Asp[1]-angiotensin I.

DOI： 10.1080/bbb.58.2244

Language：English   Publishing type：Research paper (scientific journal)  

Hydrolyzates which inhibit the angiotensin I-converting enzyme (ACE) were prepared from sardine muscle by Bacillus licheniformis alkaline protease. Considering the practical application of preparations as a functional food material, the best proteolytic conditions with respect to taste, solubility and ACE inhibitory activity were a 0.3 wt% addition of the enzyme and 17-h proteolysis at 50°C and pH 9.0. The preparations under these conditions had potent activity (IC₅₀=0.26 mg protein/ml). Fractionation of the preparations on an ODS column with ethanol resulted in the production of more potent inhibitors. The most potent activity was obtained when eluting with 10% ethanol (IC₅₀=0.015 mg protein/ml). This fraction was apparently rich in acidic amino acids, poor in hydrophobic ones, and effective for use as a physiologically functional food material by virtue of little bitterness, a fish odor and powerful ACE inhibitory activity.

DOI： 10.1271/bbb.57.922

Language：English   Publishing type：Research paper (scientific journal)  

Repository Public URL： https://hdl.handle.net/2324/7165041

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：(公社)日本農芸化学会  

SDラットにおける3-(4-ヒドロキシ-3-メトキシフェニル)プロピオン酸(HMPA)の吸収、代謝、組織への分布を解析した。HMPA(10mg/kg)を経口投与した後、血流中にHMPAとその抱合体が検出され、15分で最大に達した(HMPA 2.6nmol/mL、HMPA硫酸抱合体3.6nmol/mL、HMPAグルクロン酸抱合体0.55nmol/mL)。HMPAとその抱合体は投与6時間後に標的器官でも検出され、HMPAは迅速に抱合体に変化し、器官に広く分布すること(腎臓>肝臓>胸部大動脈>心臓>ヒラメ筋>肺)が示された。以上より、SDラットに経口投与されたHMPA(10mg/kg)は迅速に代謝され、吸収率1.2%以上で広く組織に分布することが示された。

Language：English   Publisher：Bioscience, Biotechnology and Biochemistry  

3-(4-hydroxy-3-methoxyphenyl)propionic acid (HMPA) is one of the end-products from gut microbiota from dietary polyphenols, which might contribute to their health benefits. This study aims to investigate the absorption, metabolism, and tissue accumulation of HMPA in Sprague-Dawley (SD) rats. After HMPA (10 mg/kg body weight) was orally administered, intact and conjugated HMPAs in the bloodstream were detected and reached the maximum concentration in 15 min (HMPA, 2.6 ± 0.4 nmol/mL; sulfated HMPA, 3.6 ± 0.9 nmol/mL; glucuronidated HMPA, 0.55 ± 0.09 nmol/mL). HMPA and its conjugates were also detected in the target organs 6 h postadministration, indicating that HMPA undergoes rapid conversion into conjugates, and they broadly distribute to organs with similar profiles (kidneys > liver > thoracic aorta > heart > soleus muscle > lungs). This study demonstrated that orally administered HMPA (10 mg/kg) in SD rats undergoes rapid metabolism and wide tissue distribution with ≥1.2% absorption ratio.

DOI： 10.1093/bbb/zbad023

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Language：English   Publisher：Springer  

The sweet taste receptor plays an essential role as an energy sensor by detecting carbohydrates. However, the dynamic mechanisms of receptor activation remain unclear. Here, we describe the interactions between the transmembrane domain of the G protein-coupled sweet receptor subunit, TAS1R3, and allosteric modulators. Molecular dynamics simulations reproduced species-specific sensitivity to ligands. We found that a human-specific sweetener, cyclamate, interacted with the mouse receptor as a negative allosteric modulator. Agonist-induced allostery during receptor activation was found to destabilize the intracellular part of the receptor, which potentially interfaces with the Gα subunit, through ionic lock opening. A common human variant (R757C) of the TAS1R3 exhibited a reduced response to sweet taste, in support of our predictions. Furthermore, histidine residues in the binding site acted as pH-sensitive microswitches to modulate the sensitivity to saccharin. This study provides important insights that may facilitate the prediction of dynamic activation mechanisms for other G protein-coupled receptors.

CiNii Research

Language：English   Publisher：Japanese Society for Food Science and Technology  

<p>We investigated the concentrations of halogenated flame retardants (HFRs), which include hexabromocyclododecanes (HBCDDs), polybrominated diphenyl ethers (PBDEs), and dechloranes and related compounds (DRCs), in 25 typical ready-made boxed sushi meals (each divided into seafood and non-seafood portions) using a developed simultaneous analytical method involving accelerated solvent extraction and gel permeation chromatographic separation. The developed method yielded good recoveries of surrogates (72–122 %). HBCDDs, PBDEs, and DRCs were detected in all seafood portions. While DRCs were also frequently detected in non-seafood portions, HBCDDs and PBDEs were hardly detected. The estimated dietary intakes of HBCDDs, PBDEs, and DRCs from boxed sushi meals were well below the corresponding health-based guideline values. In conclusion, our study suggests that the intake of HFRs from boxed sushi meals poses low concern for consumer health and that the developed simultaneous analytical method is highly useful for determining HFRs in seafood-based meals.</p>

DOI： 10.3136/fstr.fstr-d-22-00204

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Language：Japanese   Publisher：Editorial Board of Foods & Food Ingredients Journal of Japan  

DOI： 10.34457/ffij.227.4_376

CiNii Research

Language：English   Publishing type：Research paper (scientific journal)  

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Language：Japanese   Publisher：Society for Functional Food Research  

<p>A cognitive dysfunction is growing up year by year as a serious social issue. However, appropriate therapeutic drugs and preventive foods have not been developed yet. Thus far, it has been reported that polyphenols and peptides could improve a cognitive decline, whereas no evidence on their intact transport across the blood-brain barrier and accumulation in the brain parenchyma has been claimed. The signs of the Alzheimer's disease might be initiated 10 to 20 years before clinical definitive diagnosis, by impaired glutamate signaling at the astrocyte as well as amyloid-β accumulation in the brain. Thus, in this review we discuss the possibility of prevention of initial Alzheimer's disease by food factors.</p>

DOI： 10.32153/ffr.ffr18_p15-21

CiNii Research

Language：English   Publisher：MDPI (Multidisciplinary Digital Publishing Institute)  

A taste sensor with lipid/polymer membranes is attracting attention as a method to evaluate taste objectively. However, due to the characteristic of detecting taste by changes in membrane potential, taste sensors cannot measure non-charged bitter substances. Many foods and medicines contain non-charged bitter substances, and it is necessary to quantify these tastes with sensors. Therefore, we have been developing taste sensors to detect bitter tastes caused by non-charged substances such as caffeine. In previous studies, a sensor for detecting bitterness caused by caffeine and theobromine, theophylline, was developed, using a membrane modified with hydroxybenzoic acid (HBA) as the sensing part. The sensor was designed to form intramolecular hydrogen bonds (H-bonds) between the hydroxy group and carboxy group of HBA and to successively cause the intermolecular H-bonds between HBA and caffeine molecules to be measured. However, whether this sensing principle is correct or not cannot be confirmed from the results of taste sensor measurements. Therefore, in this study, we explored the interaction between HBA and caffeine by H^^1-nuclear magnetic resonance spectroscopy (NMR). By the H^^1 NMR detection, we confirmed that both the substances interact with each other. Furthermore, the nuclear Overhauser effect (NOE) of intermolecular spatial conformation in solution was measured, by which 2,6-dihydroxybenzoic acid (2,6-DHBA) preferably interacted with caffeine via the H-bonding and stacking configuration between aromatic rings. Identifying the binding form of 2,6-DHBA to caffeine was estimated to predict how the two substances interact.

CiNii Research

Language：English   Publisher：Journal of Agricultural and Food Chemistry  

Anthocyanins are flavonoid compounds that are natural color pigments occurring in various colored plants, such as berry fruits, vegetables, and grapes. With the elucidation of their various physiological effects, anthocyanins have been identified as promising functional food ingredients. However, findings on the bioavailability of anthocyanins, which are present in various chemical structures in foods, are limited; their intestinal absorption behaviors, including their transport route(s), have not been fully explained. This perspective overviews the current knowledge and issues and discusses advanced techniques, such as in situ matrix-assisted laser desorption/ionization mass spectrometry imaging, and future perspectives on the study of the bioavailability of anthocyanins.

DOI： 10.1021/acs.jafc.1c08207

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Publisher：ACS Applied Nano Materials  

There is no analytical system to directly and simultaneously detect taste- and odor-active compounds. Graphite carbon black (GCB) nanoparticles, a chemical adsorbent for a variety of compounds, including gaseous molecules, which consists of nanoparticles made from multilayered sheets of sp2-conjugated atomic carbon, have the characteristics required for a surface-assisted laser desorption ionization-mass spectrometry (SALDI-MS) material. Thus, in this study, GCB-LDI-MS was developed for the simultaneous detection of taste- and odor-active compounds. The proposed GCB-LDI-MS successfully detected volatile compounds, including ethyl esters, alcohols, fatty acids, and aldehydes with up to 16 carbons (maximum carbon number of the tested compounds), which could not be detected by conventional matrix-assisted-LDI-MS. Moreover, a series of taste-active compounds (e.g., amino acids and sugars) and various volatile compounds (e.g., ethyl esters, aldehydes, alcohols, fatty acids, and lactones) as a mixture in liquid samples were also detected by the present GCB-LDI-MS. Thus, the proposed simple and rapid detection technique can digitize the analysis of flavor compounds, which provides an analytical concept for flavor scanning to evaluate the palatability of food products.

DOI： 10.1021/acsanm.1c03890

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Language：English   Publisher：Japanese Society for Food Science and Technology  

<p>Polyphenols are commonly present in natural plants and serve as health benefiting food compounds. The health benefits and the metabolites of polyphenols have not yet been fully investigated because of lack of information about their bioavailability. This review was based on the previously reported literature focusing on the absorption and tissue accumulation of polyphenols. Furthermore, the physiological roles and the influx/efflux route(s) of non-absorbable polyphenols in the intestinal membrane were discussed.</p>

DOI： 10.3136/fstr.fstr-d-21-00264

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Language：English   Publishing type：Research paper (scientific journal)  

Repository Public URL： http://hdl.handle.net/2324/4772826

Language：Japanese   Publishing type：Research paper (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)  

Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide synthase, being involved in endothelial dysfunction. Furthermore, ADMA levels have been shown to predict future cardiovascular events in patients with coronary risk factors, such as diabetes and hypertension. We have previously found that glyceraldehyde-derived advanced glycation end products (glycer-AGEs) stimulate ADMA generation in vitro and the levels are associated with ADMA, endothelial dysfunction, and vascular inflammation in humans. However, it remains unclear what structurally distinct glycer-AGEs are independent correlates of ADMA. In this study, we addressed the issue. We measured serum levels of protein-bound and free methylglyoxal-derived hydroimidazolone-1 (MG-H1) and argpyrimidine, two major structurally identified glycer-AGEs by liquid chromatography-tandem mass spectrometry in 128 outpatients, and examined the correlations of these AGEs, vascular stiffness, and inflammation with ADMA. Moreover, we examined whether the changes in serum MG-H1 and argpyrimidine levels after 4-month treatment with oral hypoglycemic agents (OHAs) were associated with those of ADMA in other 44 patients with impaired glucose tolerance or type 2 diabetes. Multiple stepwise regression analysis revealed that protein-bound MG-H1, high-density lipoprotein cholesterol (inversely), high-sensitivity C-reactive protein, and cardio-ankle vascular index were independently correlated with ADMA (R² = 0.259). Treatment with OHAs significantly decreased ADMA levels in 44 glucose-intolerant or type 2 diabetic patients, and the changes in protein-bound MG-H1 levels were positively associated with those in ADMA values (p < 0.05). This study demonstrates that serum levels of protein-bound MG-H1 are independently correlated with ADMA and may be a therapeutic target for cardiovascular disease.

DOI： 10.1089/rej.2018.2152

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The present study investigated immune stimulatory effects of Cladosiphon okamuranus-derived fucoidan to activate murine macrophage-like cell line RAW264, and the functional relationship with zymosan, a Saccharomyces cerevisiae-derived β-glucan. The production of nitric oxide (NO) and tumor necrosis factor-α (TNF-α) in RAW264 cells were remarkably enhanced in the presence of 10 μg/mL fucoidan, and the stimulatory effects of fucoidan were maximally augmented in combinational treatment with 500 ng/mL zymosan, whereas any TLR ligands had no those effects. Confocal microscopic analyses suggested that fucoidan bound on plasma membrane, and it was estimated that some cell surface molecules acted as receptor for fucoidan because cytochalasin D, an inhibitor of phagocytosis, did not affect the immune enhancing activities, whereas methyl-β-cyclodextrin (MβCD), a general agent for disruption of lipid rafts, diminished that. Furthermore, it was revealed that the additive effects of zymosan on the immune activation with fucoidan was thought to be mediated by dectin-1 based on the results with dectin-1-knockdown RAW264 cells. All of results suggested that fucoidan and some kinds of β-glucan would cooperatively reinforce the activity of innate immune cells via interactive receptor crosstalk.

DOI： 10.1016/j.bbrc.2019.06.010

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Purpose: In this study, we proposed a new sensitive quantitative method for detecting helium in human blood by gas chromatography–selected-ion monitoring (SIM)-mass spectrometry (GC–SIM-MS) using naturally existing neon-21 in air as internal standard (IS). Methods: GC–SIM-MS analysis was performed on a double TC-Molsieve 5A capillary column (total length 60 m) for the separation of permanent gases by a single-run experiment. By using hydrogen as the carrier gas, the analyte (helium) and IS (neon-21) were separated on the double column, and detected at m/z 4 and 21, respectively. The ratio of the peak area of helium-to-neon-21 was used for obtaining the calibration curve for helium determination. Results: The limits of detection and quantification of helium under the present GC–SIM-MS conditions were as low as 1.8 and 6.0 ppm, respectively. The proposed GC–SIM-MS method also showed high repeatability with relative standard deviation at 1.3–5.1%, indicating that the use of neon-21 as IS was valid for reliable helium assays. The successful quantification of helium in the headspace of vacuum blood collection tubes containing the whole blood from four humans who died of helium inhalation was achieved using the proposed neon-21-aided GC–SIM-MS method; the values obtained for helium were 24–497 ppm. Conclusions: The proposed GC–SIM-MS method in combination with the naturally existing neon-21 as IS is most recommendable for quantitative assays of helium in biological samples because of its simplicity and extremely high sensitivity.

DOI： 10.1007/s11419-018-0437-6

Language：Japanese   Publishing type：Research paper (scientific journal)  

Detection of catecholamine metabolite in urine using surface plasmon resonance sensor

DOI： 10.1541/ieejsmas.139.278

Language：English   Publishing type：Research paper (scientific journal)  

Language：Japanese   Publishing type：Research paper (scientific journal)  

各種カテキン類の抗酸化作用と相乗効果について網羅的に解析した報告である。

Language：English   Publishing type：Research paper (scientific journal)  

Isomaltodextrin (IMD), a highly branched α-glucan, is a type of resistant starch. Earlier studies have indicated that polysaccharides could prevent inflammation and can be effective in reducing the complications of chronic gastrointestinal diseases such as inflammatory bowel disease (IBD). Therefore, the aim of the present study was to evaluate the anti-inflammatory effect of IMD in dextran sodium sulfate (DSS)-induced colitis in a mouse model. IMD (0.5, 1.0, 2.5, and 5.0% (w/v)) was given orally for 23 days to female Balb/c mice, and then 5% DSS was administered to induce colitis (from day 15 onward to the end of the trial). IMD could not prevent DSS-induced weight loss or colon shortening. However, IMD could reduce inflammatory cytokines, TNF-α and IL-6, in the colon. Gene expression indicated the tendency of IMD to suppress pro-inflammatory cytokines IL-1β, MCP-1, and IL-17 and to increase an anti-inflammatory cytokine, IL-10. Further study revealed that the antiinflammatory action of IMD mediates through inhibition of the expression of Toll-like receptor-4.

DOI： 10.1021/acs.jafc.6b04903

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It has previously demonstrated that adenine (6-amino-6H-purine) exhibited a vasoactive effect in contracted aorta. The adenine receptor (AdeR) has recently been identified as a G protein coupled purinergic receptor in diverse organs. It has been suggested that adenine acts as a signaling molecule through the activation of AdeR. The present study investigated the effect of adenine on endotoxin-stimulated mouse macrophages (RAW 264.7 cells) and focused on the AdeR signaling pathway. RAW 264.7 cells were treated with adenine and stimulated with lipopolysaccharide (LPS, Toll-like receptor 4 agonist) from Escherichia coli. Adenine inhibited tumor necrosis factor (TNF)-α secretion in RAW 264.7 cells. The inhibition by adenine was significantly attenuated in the presence of either adenyl cyclase (AC) or protein kinase A (PKA) inhibitors. Furthermore, adenine restored AdeR gene expression. These results firstly demonstrated that adenine acts as an anti-endotoxin compounds through a AdeR/AC/PKA signaling cascade.

DOI： 10.1016/j.jff.2016.11.013

Language：English   Publishing type：Research paper (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)  

Intrauterine fetal growth restriction (IUGR) and death (IUFD) are both serious problems in the perinatal medicine. Fetal vasculopathy is currently considered to account for a pathogenic mechanism of IUGR and IUFD. We previously demonstrated that an innate immune receptor, the nucleotide-binding oligomerization domain-1 (Nod1), contributed to the development of vascular inflammations in mice at postnatal stages. However, little is known about the deleterious effects of activated Nod1 signaling on embryonic growth and development. We report that administration of FK565, one of the Nod1 ligands, to pregnant C57BL/6 mice induced IUGR and IUFD. Mass spectrometry analysis revealed that maternally injected FK565 was distributed to the fetal tissues across placenta. In addition, maternal injection of FK565 induced robust increases in the amounts of CCL2, IL-6, and TNF proteins as well as NO in maternal, placental and fetal tissues. Nod1 was highly expressed in fetal vascular tissues, where significantly higher levels of CCL2 and IL-6 mRNAs were induced with maternal injection of FK565 than those in other tissues. Using Nod1-knockout mice, we verified that both maternal and fetal tissues were involved in the development of IUGR and IUFD. Furthermore, FK565 induced upregulation of genes associated with immune response, inflammation, and apoptosis in fetal vascular tissues. Our data thus provided new evidence for the pathogenic role of Nod1 in the development of IUGR and IUFD at the maternal-fetal interface.

DOI： 10.4049/jimmunol.1500295

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Catecholamine synthesis and transmission in the brain are influenced by the availability of Tyr in the body. In this study, we compared the effects of oral administration of Tyr-containing dipeptides Ile-Tyr, Ser-Tyr, and Tyr-Pro with Tyr alone on catecholamine metabolism in the mouse brainstem. Among these dipeptides, Ile-Tyr administration led to increases in dopamine, the dopamine metabolites homovanillic acid, and 3,4-dihydroxyphenylacetic acid, compared to administration of Ser-Tyr, Tyr-Pro, or Tyr alone. In comparison, administration of Ser-Tyr induced significantly increasing noradrenaline turnover, while Tyr-Pro administration suppressed dopamine turnover. Therefore, oral administration of Ile-Tyr, Ser-Tyr, and Tyr-Pro differentially affected metabolism of dopamine and noradrenaline. These observations strongly suggest that Tyr-containing dipeptides exert distinct effects on catecholamine metabolism in the brainstem when ingested orally.

DOI： 10.1155/2016/6020786

Language：English   Publishing type：Research paper (scientific journal)  

Trp-His, the anti-atherosclerotic dipeptide, exerted an antiproliferative effect on vascular smooth muscle cells by L-type Ca²⁺ channel blocker-like effect. The beneficial potential by the blockade of Ca²⁺ channels on chronic intestinal inflammation, including inflammatory bowel disease (IBD), is unclear. Trp-His (100 or 250 mg/kg body weight/day) was administered for 14 days to BALB/c mice, and 5% dextran sodium sulfate (DSS) was administered to induce colitis in the last 7 days. Trp-His reduced DSS-induced typical colitis symptoms and cytokine expression in the colon. Trp-His inhibited interleukin (IL)-8 secretion in tumor necrosis factor (TNF)-α-stimulated HT-29 cells. The inhibitory effect of Trp-His, as well as that of Ca²⁺ channel blockers, was impaired by the presence of Ca²⁺ channel agonist Bay K 8644. The TNF-α-induced activation of mitogen-activated protein kinases (MAPKs) and IκBα were decreased by Trp-His. These results indicated that the anti-inflammatory effect of Trp-His may be involved in the blockade of L-type Ca²⁺ channels.

DOI： 10.1021/acs.jafc.5b01682

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1021/jf505248n

Language：English   Publishing type：Research paper (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)  

We manufactured a new fermented tea by tea-rolling processing of third crop green tea (Camellia sinensis) leaves and unripe satsuma mandarin (Citrus unshiu) fruits, and investigated the effects of feeding the tea extract on serum and liver lipid concentrations in rats. The tea extract contained narirutin and hesperidin from unripe satsuma mandarin fruits, catechins from green tea leaves, and black tea polyphenols produced by oxidation of catechins. The fermented tea extract inhibited pancreatic lipase activity in vitro. When rats were fed diets supplemented with the freeze-dried tea extract (0.50% or 0.75%) for 4 weeks, hepatic triglyceride and cholesterol concentrations were reduced in a dose-dependent manner, and the reductions were significant in rats fed diet composed of 0.75% tea extract compared to those fed the control diet. These results suggest that the tea produced by mixing third crop green tea leaves and unripe satsuma mandarin fruits has a hypolipidemic property.

DOI： 10.3136/fstr.21.77

Language：English   Publishing type：Research paper (scientific journal)  

The di-peptide Trp-His (WH) has vasorelaxant and anti-atherosclerotic functions. We hypothesized that WH has multiple biological functions and may aid AMP-activated protein kinase (AMPK) activation and affect the glucose transport system in skeletal muscle.First, we examined whether WH or His-Trp (HW) can activate AMPKα. Treatment of L6 myotubes with WH or HW significantly increased phosphorylation of AMPKα. WH activated AMPK independently of insulin and significantly increased glucose uptake into L6 myotubes following translocation of glucose transporter 4 (Glut4) to the plasma membrane. This activation was induced by the LKB1 pathway but was independent of changes in intracellular Ca²⁺ levels and the Ca²⁺/calmodulin-dependent kinase pathway. L6 myotubes express only one type of oligopeptide transporter, peptide/histidine transporter 1 (PHT1, also known as SLC15a4), and WH is incorporated into cells and activates AMPKα following PHT1-mediated cell uptake.These findings indicate that (1) WH activates AMPK and insulin independently enhances glucose uptake following translocation of Glut4 to the plasma membrane, (2) activation of AMPKα by WH is mediated by the LKB1 pathway, without altering the Ca²⁺-dependent pathway, and (3) L6 myotubes express only one type of peptide transporter (PHT1; SLC15a4), which incorporates WH into cells to activate AMPKα.

DOI： 10.1016/j.fob.2014.10.008

Language：English   Publishing type：Research paper (scientific journal)  

Language：Japanese   Publishing type：Research paper (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)  

Highly sensitive detection of small peptides at the pM level was achieved by liquid chromatography-multiple reaction monitoring-tandem mass spectrometry (LCMRM- MS/MS) in combination with the 2,4,6-trinitrobenzene sulfonate (TNBS) conversion technique. Six di-peptides having Tyr at the C-terminal (i.e., Gly-Tyr, Val-Tyr, Met-Tyr, Glu-Tyr, Lys-Tyr and His-Tyr) were subjected to the TNBS-MRM analysis in this study. The TNBS conversion conditions of pH 8.0, 30 °C and 60- min incubation enabled the di-peptides to be successfully converted to a trinitrophenyl (TNP) form with the mass increment of +212 Da. The proposed TNBS-MRM method enabled di-peptide detection that was highly improved by a factor of 3-55 in signal-to-noise ratio due to increased hydrophobicity by the induced TNP moiety. The method also permitted highly sensitive detection of di-peptides with a detection limit of >54 pM (>1:35 fmol/injection), achieving high reproducibility (<5%coefficient of variation) and rapidity (<30 min) by LC-MRM-MS/MS.

DOI： 10.1271/bbb.130448

Language：English   Publishing type：Research paper (scientific journal)  

Although tea polyphenols are reported to improve serum glucose and lipid levels by inhibiting amylase activity and reducing lipid absorption, in vivo data are lacking. We evaluated in vivo the antihyperglycemic and hypotriacylglycerolemic effects of theaflavins (TFs) and theasinensin A (TSA) refined from fermented tea to purities of 12 and 59%, respectively. Feeding male KK-A^y mice diets with 0.1% TFs or TSA for 6 weeks reduced serum glucose levels by >30% compared to a control diet. Rats fed diets containing 0.2% TFs or TSA for 4 weeks had higher fecal fat excretion and 33% lower hepatic triacylglycerol; hepatic fatty acid synthase activity was not affected. Oral administration of TFs or TSA reduced the increase in serum triacylglycerol after an oral bolus of a fat emulsion. These results indicate TFs and TSA induce antihyperglycemic responses in diabetic mice and are hypotriacylglycerolemic in rats by suppressing intestinal fat absorption.

DOI： 10.1021/jf400123y

Language：Japanese   Publishing type：Research paper (scientific journal)  

Language：Japanese   Publishing type：Research paper (scientific journal)  

We kneaded third-crop green tea and loquat leaves and prepared them by a firing process in order to manufacture a new fermented tea mix. Sensory testing was carried out and aromatic compounds were measured during the firing stage in order to investigate the effects of temperature and time on the tea product. The firing process did not alter the contents of the major aromatic chemicals in the tea mix. On the other hand, levels of (E,E)-2, 4-heptadienal, an unfavorable aromatic chemical found in low-grade tea leaves, decreased with increases in both temperature and time. Aromatic compounds increased only when firing was carried out at higher temperatures and for longer periods. The firing process does not typically enhance favorable flavors of third-crop teas. However, this study demonstrated that firing can enhance heat-induced aromatic compounds, thereby making it suitable for firstcrop green tea processing.

DOI： 10.3136/nskkk.60.110

Language：English   Publishing type：Research paper (scientific journal)  

Background: Inflammatory bowel disease (IBD) is a chronic inflammation of the gastrointestinal tract. The peptide transporter PepT1 is responsible for the intestinal uptake of dietary peptides, and its expression in the gastrointestinal tract is up-regulated during intestinal inflammation, indicating that PepT1 may be a promising target for IBD therapeutics. Methods: The transport of soy-derived di- and tripeptides across Caco-2 intestinal epithelial cells was examined, and the anti-inflammatory effects of the transported peptide VPY were evaluated in vitro in Caco-2 and THP-1 macrophages, and in vivo in a mouse model of DSS-induced colitis. Results: VPY inhibited the secretion of IL-8 and TNF-α, respectively, from Caco-2 and THP-1 cells. VPY transport and anti-inflammatory activity in Caco-2 cells was reduced in the presence of Gly-Sar, indicating this activity was mediated by PepT1. In mice, VPY treatment reduced DSS-induced colitis symptoms and weight loss, improved colon histology, reduced MPO activity, and decreased gene expression of the pro-inflammatory cytokines TNF-α, IL-6, IL-1β, IFN-γ and IL-17 in the colon. Conclusions and general significance: VPY is a novel PepT1 substrate that can inhibit the production of pro-inflammatory mediators in vitro in intestinal epithelial and immune cells, and reduce the severity of colitis in mice by down-regulating the expression of pro-inflammatory cytokines in the colon, suggesting that VPY may be promising for the treatment of IBD.

DOI： 10.1016/j.bbagen.2012.07.007

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The aim of this study was to demonstrate the enhancement of the vasorelaxation power of the antiatherosclerotic voltage-dependent L-type Ca ²⁺ channel (VDCC)-blocking peptide Trp-His by epigallocatechin gallate (EGCg). We found that 300 μM EGCg dramatically enhanced the magnitude of Trp-His-induced vasorelaxation by a factor of >6 (EC₅₀ of Trp-His: EGCg(-), 2.80 ± 0.05 mM; EGCg(+), 0.45 ± 0.04 mM) in phenylephrine-contracted rat aorta. The enhancing effect of EGCg was completely abolished in endothelium-removed aorta and high K⁺-contracted aorta. The enhancement of Trp-His-induced vasorelaxation by EGCg was significantly diminished by either N^G-monomethyl-l-arginine acetate (NO synthase (NOS) inhibitor) or 1-H-[1,2,4]oxadiazolo[4,3]quinoxalin-1-one (soluble guanylyl cyclase inhibitor), together with the enhancement of NOS activity by EGCg. These results indicate that the enhancing effect of EGCg in Trp-His-induced vasorelaxation may be involved in the activation of NO/cGMP pathway.

DOI： 10.1021/jf3010228

Language：English   Publishing type：Research paper (scientific journal)  

The aim of this study is to illustrate the in vivo and in vitro absorption of theasinensins B and A that are (-)-epigallocatechin-3-O-gallate (EGCG)-(-)-epigallocatechin (EGC) dimer and EGCG dimer, respectively, and their transport pathway across the intestinal membrane. Our animal study by a single oral administration to rats demonstrated the intact absorption of theasinensins into the blood system, which was estimated to be a >10-fold lower absorption amount than EGCG. The in vitro absorption study indicated that theasinensins can be transported across Caco-2 cell monolayers, while their permeability coefficients were also >10-fold lower than those of EGCG and EGC. Transport experiments using cytochalasin D or quercetin as a tight junction (TJ) modulator and a non-saturable permeation revealed that theasinensins were transported across Caco-2 cells in a TJ paracellular diffusion route. In conclusion, the dimers of condensed catechins, theasinensins B and A, can be absorbed intact into rat blood and transported across Caco-2 cell monolayers probably through a TJ paracellular pathway.

DOI： 10.1021/jf302242n

Language：English   Publishing type：Research paper (scientific journal)  

Apple procyanidins (AP), one of the polyphenol-rich compounds, showed an endothelial-dependent vasorelaxation in rat aorta, but the mechanisms of beneficial effects are still unclear. The present study was designed to clarify the potential role of AP in rat aorta endothelial cells (RAECs). The treatment of RAECs with AP (1-10 μg/ml) resulted in a dose-dependent hyperpolarization with a maximum effect at 10 μg/ml, and for this reason, AP (10 μg/ml) was used in all the following experiments. AP-induced hyperpolarization was significantly inhibited by pretreatment of nonspecific K ⁺ inhibitor, tetraethyl ammonium chloride or specific K ⁺ channel inhibitors, iberiotoxin, glibenclamide, 4-aminopyridine and BaCl ₂, as well as by high KCl or Ca ²⁺-free solution. AP-induced hyperpolarization was also proved using 64-channel multielectrode dish system that can monitor a direct and real-time change of membrane potential. Furthermore, AP treatment caused a significant increase of nitric oxide (NO) production and cyclic guanosine monophosphate levels via endothelial NO synthase messenger RNA expression. The NO production was inhibited by N ^G-monoethyl-l-arginine or Ca ²⁺-free solution and was completely abolished by their combination. Also, AP inhibited endothelial proliferation, while the effect was significantly abolished by N ^G-monoethyl-l-arginine or tetraethyl ammonium chloride. These findings suggest that AP induces both hyperpolarization of RAECs via multiple activation of K ⁺ channels and activation of NO/cyclic guanosine monophosphate pathway via increasing NO production or is responsible for antiangiogenic effect. Diminishment of hyperpolarization as well as NO production of AP in Ca ²⁺-free solution implicated that AP would play a crucial role in promoting Ca ²⁺ influx into endothelial cells so as to promote both actions.

DOI： 10.1016/j.jnutbio.2010.12.005

Language：Japanese   Publishing type：Research paper (scientific journal)  

The third crop of green tea leaves contains a relatively large amount of catechins, resulting in a bitter taste to the hot-water extract of its leaves. On the other hand, loquat leaves have a strong enzymatic activity that can oxidize catechins. They also contain chlorogenic acid, which accelerates the oxidation of catechins. Thus, we tried to promote the oxidative polymerization of catechins in third-crop green tea leaves by the addition of loquat leaves, and presumed that the taste of the third-crop green tea would be improved. However, the active ingredients contained in loquat leaves are difficult to extract with hot water due to the hardness of the leaves. Thus, we mixed and kneaded the third-crop green tea leaves and loquat leaves together using the tea roller of a tea manufacturing machine, which may have facilitated the elution of the components contained in loquat leaves, and may have effectively promoted the oxidation of catechins contained in the third-crop green tea. In this study, we improved the conventional method of producing black tea leaves, and developed a method for producing new high-quality mixed and fermented tea using the third crop of green tea leaves and loquat leaves, which were previously unused resources. We outline our main eforts here.

DOI： 10.3136/nskkk.58.403

Language：English   Publishing type：Research paper (scientific journal)  

Phenolic constituents of a new functional fermented tea produced by tea-rolling processing of a mixture (9:1) of tea leaves and loquat leaves were examined in detail. The similarity of the phenolic composition to that of black tea was indicated by high-performance liquid chromatography comparison with other tea products. Twenty-five compounds, including three new catechin oxidation products, were isolated, and the structures of the new compounds were determined to be (2R)-2-hydroxy-3-(2,4,6-trihydroxyphenyl)-1-(3,4,5- trihydroxyphenyl)-1-propanone 2-O-gallate, dehydrotheasinensin H, and acetonyl theacitrin A by spectroscopic methods. In addition, theacitrinin A and theasinensin H were obtained for the first time from commercial tea products. Isolation of these new and known compounds confirms that reactions previously demonstrated by in vitro model experiments actually occur when fresh tea leaves are mechanically distorted and bruised during the production process.

DOI： 10.1021/jf201499n

Language：Japanese   Publishing type：Research paper (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)  

Background: Soy protein and soy peptides have attracted considerable attention because of their potentially beneficial biological properties, including antihypertensive, anticarcinogenic, and hypolipidemic effects. Although soy protein isolate contains several bioactive peptides that have distinct physiological activities in lipid metabolism, it is not clear which peptide sequences are responsible for the triglyceride (TG)-lowering effects. In the present study, we investigated the effects of soy protein-derived peptides on lipid metabolism, especially TG metabolism, in HepG2 cells and obese Otsuka Long-Evans Tokushima fatty (OLETF) rats. Results: In the first experiment, we found that soy crude peptide (SCP)-LD3, which was prepared by hydrolyze of soy protein isolate with endo-type protease, showed hypolipidemic effects in HepG2 cells and OLETF rats. In the second experiment, we found that hydrophilic fraction, separated from SCP-LD3 with hydrophobic synthetic absorbent, revealed lipid-lowering effects in HepG2 cells and OLETF rats. In the third experiment, we found that Fraction-C (Frc-C) peptides, fractionated from hydrophilic peptides by gel permeation chromatography-high performance liquid chromatography, significantly reduced TG synthesis and apolipoprotein B (apoB) secretion in HepG2 cells. In the fourth experiment, we found that the fraction with 0.1% trifluoroacetic acid, isolated from Frc-C peptides by octadecylsilyl column chromatography, showed hypolipidemic effects in HepG2 cells. In the final experiment, we found that 3 di-peptides, Lys-Ala, Val-Lys, and Ser-Tyr, reduced TG synthesis, and Ser-Tyr additionally reduced apoB secretion in HepG2 cells. Conclusion: Novel active peptides with TG-lowering effects from soy protein have been isolated.

DOI： 10.1186/1476-511X-10-85

Language：English   Publishing type：Research paper (scientific journal)  

Absorption and metabolism of a natural compound, 6-O-caffeoylsophorose (CS) from acylated anthocyanins in a red vinegar fermented with purple sweetpotato, were clarified. The absorption of CS and conjugated CS in blood from orally administrated Sprague-Dawley rats at a dose of 400 mg/kg was investigated by electrochemical detection-high performance liquid chromatography. As a result, CS was successfully detected in rat plasma (AUC_0-6h, 108.6 ± 8.1 nmol h/mL) and was found to be an intact absorbable polyphenol. In addition, half of the absorbed CS was detected as its conjugates (AUC_0-6h, 50.7 ± 5.7 nmol h/mL) as well as caffeic and ferulic acids from CS. By a time-of-flight-mass spectrometric analysis of CS-administered plasma sample, glucuronide and methylated conjugates of CS were identified, in addition to glucuronide, methylated, or sulfate conjugates of caffeic and ferulic acids. Consequently, CS was absorbed in intact form into rat blood and partly degraded to caffeic and ferulic acids or metabolized by glucuronidation, methylation, or sulfatation.

DOI： 10.1021/jf200764d

Language：English   Publishing type：Research paper (scientific journal)  

Chungkookjang is a Korean fermented soybean containing microorganisms, proteinase, and diverse bioactive compounds, including a high concentration of isoflavones and peptides. Growth of breast cancer MCF7 cells decreased dependent on the concentration of fermented soybean extracts. The effect of fermented soybean on cellular gene expression was determined in a systematic manner comprehensively. DNA microarray analysis was performed using 25,804 probes. Ninety one genes whose expression levels were significantly changed were selected. TGFβI and Smad3 were upregulated. Downregulation of inflammation-related CSF2, CSF2RA, and CSF3 was found. Differential expression of chemokines CCL2, CCL3, CCL3L3, CXCL1, and CXCL2 were observed. Network analysis identified ERβ in the network. Based on the experimental results, taking fermented soybean might be helpful for preventing breast cancer by a mechanism activating TGFβ pathway and depressing inflammation.[Supplemental materials are available for this article. Go to the publisher's online edition of Nutrition and Cancer for the following free supplemental resources: Detailed table showing the full list of genes and their analysis details.]

DOI： 10.1080/01635581.2011.551987

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Fourteen anthocyanins were detected in the flowers of R. simsii distributed in Vietnam and Japan. The anthocyanin constituents of R. simsii flowers seem to be more complex in the Japanese than Vietnamese population. The percentage of each flower anthocyanin was very low except for two major anthocyanins found in all Vietnamese and Japanese accessions. It was not possible to classify the Vietnamese and Japanese populations by flower anthocyanin constituents. The two major anthocyanins found in all accessions of R. simsii flowers in Vietnam and Japan were isolated and purified by column and high-performance liquid chromatography. Their structures were elucidated by 1H-NMR spectroscopic analyses and either acid or alkaline hydrolysis, and they were identified as cyanidin 3-galactoside and cyanidin 3-arabinoside. These two anthocyanins seem to be common to red-flowered evergreen azaleas, such as R. indicum, R. kaempferi, R. oldhamii, and R. scabrum. JSHS

Language：English   Publishing type：Research paper (scientific journal)  

Our previous findings regarding the biological activities of small peptides revealed that a di-peptide, Trp-His (WH), could play a role in the prevention of vascular lesions, including cell proliferation and atherosclerosis. Its vasoprotective effects could be associated with suppression of the vasocontraction signaling cascade, but the underlying mechanism(s) remains obscure. In this study, we attempted to elucidate the vasoprotective mechanism of WH, in opposing the proliferation of rat vascular smooth muscle cells (VSMCs). In VSMCs from 8 week-old male Wistar rat thoracic aortae, WH evoked a significant dose-dependent anti-proliferation effect, without cytotoxicity. In mitogen-stimulated cell experiments, 300 μM WH inhibited cytosolic Ca ²⁺ elevation in VSMCs induced by 10 μM angiotensin II (Ang II). Furthermore, WH suppressed extracellular Ca²⁺ entry into CaCl ₂-stimulated VSMCs. The biological capacity of WH as an intracellular Ca²⁺ ([Ca²⁺]_i) suppressor was also proven when 50 μM Bay K8644 was used to enhance Ca²⁺ entry via a voltage-dependent l-type Ca²⁺ channel (VDCC) and 300 μM WH elicited a 23% reduction in [Ca²⁺]_i. The absence of a reduction of the [Ca²⁺]_i by the mixture of tryptophan and histidine revealed the importance of the peptide backbone in the [Ca ²⁺]_i reduction effect. Furthermore, the WH-induced [Ca²⁺]_i reduction was abolished by verapamil, but not by nifedipine, indicating that WH likely binds to an extracellular site of the VDCC at a site similar to that of the dihydropyridine type-Ca²⁺ channel blockers.

DOI： 10.1016/j.peptides.2010.07.013

Language：English   Publishing type：Research paper (scientific journal)  

Repository Public URL： https://hdl.handle.net/2324/7168381

Language：English   Publishing type：Research paper (scientific journal)  

Language：Japanese   Publishing type：Research paper (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)  

Background: In the field of food science, much interest has been focused on the development of alternative medicinal foods with the ability to regulate excess blood glucose level (BGL) rise. The authors have successfully developed a new fermented tea product (LG tea) by co-fermentation of loquat (Eriobotrya japonica) leaf and summer-harvested green tea leaf. The objective of this study was to examine the acute suppression effect of LG tea on BGL rise in disaccharide-loaded Sprague-Dawley (SD) rats and to evaluate its possible usage as an antidiabetic functional food material. Results: As a result of single oral administration of hot water extract of LG tea (50 mg kg^-1) to maltose-loaded SD rats, BGL at 30 min was significantly decreased by 23.8% (P < 0.01) compared with the control. A corresponding reduction in serum insulin secretion was also observed. The ED₅₀ value of LG tea (50.7 mg kg^-1) was estimated to be about 16-fold higher than that of the therapeutic drug acarbose (3.1 mg kg^-1). Conclusion: No significant change in BGL was observed when sucrose or glucose was administered, suggesting that the suppression effect of LG tea was achieved by maltase inhibition, not by sucrase inhibition or glucose transport inhibition at the intestinal membrane.

DOI： 10.1002/jsfa.3883

Language：English   Publishing type：Research paper (scientific journal)  

Most of the investigations for an alternative medicinal treatment on atherosclerosis have been focused on natural or dietary compounds including phytochemicals. So far, few studies regarding anti-atherosclerotic small peptides except for tetrapeptide of Lys-Arg-Glu-Ser have been reported. The present study was, thus, to investigate whether dipeptide Trp-His, which is one of vasodilating small peptides, could reduce atherosclerotic lesions in apo E-deficient mice fed a high-fat diet. The animal study involved a 9-week-successive administration of Trp-His at a dose of 0, 10 or 100mg/kg per d. After 9-week administration, en face analyses provided the first direct evidence that the atherosclerotic lesion area was significantly reduced by 27 and 38% for Trp-His dosed at 10 and 100mg/kg per d, respectively, compared with the control group. Administration of Trp-His did not affect growth parameters such as body weight and feeding efficiency (P>01). Total serum cholesterol and HDL-cholesterol as well as lipid profiles in the liver did not differ between the tested groups. Taken together, the anti-atherosclerotic effect of dipeptide Trp-His should be addressed into physiological functions of bioactive peptides, in which the dipeptide may elicit the power by alternative mechanism(s), not by the regulation of lipid metabolism.

DOI： 10.1017/S0007114509991814

Language：Japanese   Publishing type：Research paper (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)  

In this study, we evaluated the antioxidant activity (diphenylpicrylhydrazyl (DPPH)-radical scavenging activity) of the low-molecular weight fraction of water-soluble Susabinori (Porphyra yezoensis) extract (LMF). DPPH-radical scavenging activity of LMF (65.5 μmol-Trolox eq/ml) was enhanced at temperatures over 100 °C (1.4, 2.0 and 2.4 times higher at 100, 110 and 120 °C, respectively). As a result of HPLC separations, a newly produced peak was observed in heat treated LMF, while a marked decrease of another peak was found after heat treatment of LMF. The decreased peak was identified as porphyra-334, which is a typical mycosporine-like amino acid, by ESI/MSⁿ analysis (protonated molecule [M + H]⁺ at m/z 347.1 and its fragment ion 303.1). The newly produced compound with [M + H]⁺ at m/z 329.1 was found to be a dehydrated compound of porhyra-334. The compound exhibited an extremely high-IC₅₀ value of 10.1 μg/ml in DPPH-radical scavenging activity, compared to porphyra-334 (>1000 μg/ml).

DOI： 10.1016/j.foodchem.2008.08.087

Repository Public URL： https://hdl.handle.net/2324/7168675

Language：English   Publishing type：Research paper (scientific journal)  

α-Glucosidase (AGH) from the small intestine of rat was immobilized onto a glutaradehyde (GA) activated NH₂-96 well microplate to establish a convenient and rapid AGH inhibition assay system. After AGH immobilization, remaining GA groups were blocked by β-alanine to induce a negative charge on the surface of the well. The AGH-plate showed an enzyme activity of 444 nU/well under an assayed condition at 37°C for 2 h using 0.3 mM 4-methylumbelliferyl-α-D- glucopyranoside as a fluorogenic substrate. Inhibitory powers of voglibose and acarbose as therapeutic AGH inhibitors were successfully evaluated to have IC₅₀ values of 13 and 114 nM, respectively. 2009

DOI： 10.2116/analsci.25.559

Language：Japanese   Publishing type：Research paper (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)  

The aim of this study was to point out the potential of tartary buckwheat on vascular functions. A nonabsorbed fraction of hot-water extract of tartary buckwheat on a SP70 column (TBSP-T), which was free from rutin, was used for this aim. In a contractile experiment using Sprague-Dawley rat thoracic aorta rings contracted by 1.0 μM phenylephrine (PE) or 50 mM KCl, TBSP-T evoked a significant vasorelaxation [EC₅₀ (mg/ml): PE; 2.2; KCl, 1.9]. By a further fractionation of TBSP-T by liquid-liquid partitioning into basic, neutral and acidic fractions, a marked enhancement of vasorelaxation effect was observed only for acidic fraction (EC₅₀, 0.25 mg/ml). The action of acidic fraction was significantly attenuated in endothelium-denuded aortic rings and in the presence of nitric oxide synthase inhibitor, N^G-monomethyl-l-arginine (100 μM). The fraction also enhanced the cyclic guanosine monophosphate (cGMP) production in aortic rings contracted with PE [cGMP (pmol/mg protein): PE, 7.2±2.3; PE+Acidic fraction, 35±8]. These results indicate that acidic fraction could mediate NO/cGMP pathways, thereby exerting endothelium-dependent vasorelaxation action. In conclusion, tartary buckwheat was proven to regulate vascular tones and have latent acidic candidates except for rutin.

DOI： 10.1016/j.jnutbio.2007.09.005

Language：English   Publishing type：Research paper (scientific journal)  

To evaluate the duration of antihyperglycemic effects of 6-O-caffeoylsophorose (CS), a newly identified natural α-glucosidase inhibitor from fermented purple-sweet potato, a single oral administration of CS was given to maltose-loaded Sprague-Dawley rats. Administration of CS (200 mg/kg) 30 min or 60 min before maltose administration produced an elevation of blood glucose level by administration of 2 g/kg of maltose in rats that was significantly lower than for no administration (control). In contrast, simultaneous or pro-administration of CS with maltose eliminated the antihyperglycemic effect. CS significantly reduced rat intestinal α-glucosidase activity in all of the small intestinal mucosal regions with a maximal reduction ratio of ca. 40% up to 60 min after CS administration. Thereafter, the intestinal α-glucosidase activity tended to return to basal level. These findings suggest that the antihyperglycemic effect of CS is restricted to pre-administration within 60 min.

DOI： 10.3136/fstr.14.477

Repository Public URL： https://hdl.handle.net/2324/7169334

Language：English   Publishing type：Research paper (international conference proceedings)  

Anthocyanins are polyphenolic glycoside pigments widely distributed in the plant kingdom. Recently, along with health trend against aging, anthocyanins have attracted much attention as functional food factors that prevent life-style related diseases. To develop new stable anthocyanin materials, we elucidated a correlation between the structures and the functionalities of acylated anthocyanins with two or more aromatic acids in the plant materials such as a purple sweet potato storage root and a butterfly-pea flower. Of the functionalities, the antioxidative activity was evaluated on the basis of DPPH radical scavenging activity and lipid peroxidation inhibitory activity. It was demonstrated that aglycone and/or aromatic acids with free phenolic hydroxyl groups on neighboring positions and only aromatic acids at outer sides in polyacylated anthocyanin molecules (folded in solutions) were more effective for the antioxidative activity.

DOI： 10.1021/bk-2008-0993.ch009

Language：English   Publishing type：Research paper (scientific journal)  

Enzymatic hydrolysis of the protein from an edible insect species, the cotton leafworm Spodoptera littoralis (Lepidoptera) leads to the release of angiotensin I converting enzyme (ACE) inhibitory peptides. The subsequent hydrolysis with pepsin, trypsin and α-chymotrypsin was designed to simulate the human gastrointestinal digestion process. After fractionation of this hydrolysate using consecutive chromatographic techniques, including size exclusion chromatography and reverse-phase high-performance liquid chromatography, a new ACE inhibitory tripeptide was identified. The amino acid sequence of the tripeptide was determined as Ala-Val-Phe and the in vitro ACE inhibitory activity assay revealed an IC₅₀ value of 2123 μM.

DOI： 10.1016/j.procbio.2008.04.014

Language：Japanese   Publishing type：Research paper (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)  

The goal of this study was to elucidate the structure-activity relationship for vasodilating peptides and their underlying mechanism. In this study, we synthesized 62 di- and tri-peptides having aromatic amino acid residues (Tyr, Trp and Phe). Among them, only 4 peptides (HW, WH, WL and WV) evoked an apparent vasodilating effect in 50 mM KCl-contracted aortic rings in the descending order of WH>HW>WL>WV; WH showed the vasodilating activity with an EC₅₀ of 3.4 mM. Within our experimental results, it seems likely that Trp residue at the N-terminal would play a role in eliciting vasodilating effect. No appearance of vasodilating effect for stereoisomers of WH with D-configuration revealed that the vessel would recognize the l-configuration of WH. The presence of angiotensin I-converting enzyme (ACE) inhibitor (50 nM enalaprilat) did not affect the WH-induced vasodilating effect, though WH showed a slight ACE inhibitory activity (IC₅₀: 93 μM). The effect was also observed in the endothelium-denuded aortic rings. In contrast, WH provoked a significant displacement to the right in the vasodilating curve in the presence of 30 nM verapamil, while no shift was observed in the presence of 2.5 nM nifedipine. These results indicate that WH, a vasodilating di-peptide, would exert a vasodilation via the suppression of Ca²⁺ influx into KCl-induced depolarized aortic rings. The present study also suggests that the binding site of WH to the Ca²⁺ channel may be competitive to that of phenylalkylamine-type voltage-gated L-type Ca²⁺ channel blocker.

DOI： 10.1016/j.lfs.2008.02.001

Language：English   Publishing type：Research paper (scientific journal)  

The chemical composition of the essential oil from the leaves of Acacia tortilis, collected from Ogbomoso, Nigeria, was analyzed by means of GC-FID and GC/MS. Seventy-five compounds were identified. The oil was dominated by a large amount of sesquiterpenoid compounds (52.2%). The major components of the oil were α-humulene (12.0%), α-cadinol (10.6%), nerolidol (9.9%), γ-cadinene (7.4%) and 2-(E)-octenal (6.0%).

DOI： 10.1080/10412905.2008.9699969

Language：Japanese   Publishing type：Research paper (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)  

A replicate heart-cut column-switching HPLC method combined with two switching valves was newly developed for the simultaneous determination of three antihypertensive peptides (Ala-Phe, Tyr-Pro, and Trp-Tyr) in tryptic casein hydrolysate in one run-in assay. After a first separation on an octadecyl silane (ODS) column, heart-cuts of each peptide were individually separated on a subsequent analytical ODS column: 26% acetonitrile for Ala-Phe and Tyr-Pro (32% for Trp-Tyr) in 0.1% trifluoroacetic acid containing 10 mM sodium 1-octanesulfonate at 0.8 mL/min. Ala-Phe, Tyr-Pro, and Trp-Tyr in casein hydrolysate were determined within 70 min to be 0.377 ± 0.037 mg/g, 2.50 ± 0.26 mg/g, and 0.096 ± 0.008 mg/g, respectively.

DOI： 10.1021/jf0720584

Language：English   Publishing type：Research paper (scientific journal)  

Four Nigerian medicinal plants used for the treatment of various ailments in traditional ethnomedicine were evaluated for their anti-diabetic potential. The plants Irvingia gabonensis (O'Rorke) Bail, Eucalyptus torreliana F.v. Muell, Securidata longependuculata Fers and Murraya panicutata (L.) Jack were used in the study. Only the aqueous extract of I. gabonensis exhibited a potent maltase-inhibitory activity with an IC₅₀ of O.10mg/mL, as well as a sucrase-inhibitory activity (IC₅₀ of O.llmg/mL), whereas α-amylase inhibitory activity was quite poor (IC₅₀ of 0.53 mg/mL). A significant lowering of the blood glycemie response to maltose ingestion in 8-week old Sprague-Dawley rats was observed at a dose of 300 mg/kg, in response to significant reduction in postprandial insulin response level.

DOI： 10.3136/fstr.13.169

Language：Japanese   Publishing type：Research paper (scientific journal)  

A succesive determination of anthocyanins in purple sweet potato

Language：English   Publishing type：Research paper (scientific journal)  

Some di-peptides have been proven to exert an antihypertensive effect in mild-hypertensive subjects. The aim of this study was to clarify whether combined administration of an ACE inhibitor, captopril, with an antihypertensive di-peptide Val-Tyr (VY) would alter their potent antihypertensive effects in spontaneously hypertensive rats (SHRs). Single oral administration of captopril (2.5 mg/kg), VY (25 mg/kg), or captopril (2.5 mg/kg) + VY (25 mg/kg) to 18-week-old male SHRs was performed. Systolic blood pressure (SBP) was measured up to 9 h, and plasma captopril concentrations were determined. A transport study of captopril and/or VY across living rat jejunum from SHRs was also performed to evaluate the kinetics of absorption. Combined administration of captopril with VY failed to lower the BP during the 9-h experiment. A transport study of captopril or VY revealed that VY inhibited captopril transport, and vice versa, in a competitive manner and exhibited an approximately 1/3-fold lower Ki value for captopril compared with that for VY; indicating that both compounds compete for the same membrane transport pathway. A 50% decrease in plasma captopril levels by combined administration with VY supported that the attenuation of the BP lowering effect was due to inhibition of captopril uptake by VY. Consequently, our findings suggest that subjects treated with ACE inhibitors for hypertension should avoid combined-intake with antihypertensive foods that are rich in small peptides due to the competitive inhibition of drug uptake by these peptides.

DOI： 10.1016/j.lfs.2006.08.013

Language：English   Publishing type：Research paper (scientific journal)  

In this study, we found that antihypertensive di-peptide Val-Tyr (VY) showed a vascular relaxation effect in KCl-induced contraction of thoracic aorta rings from 18-week-old spontaneously hypertensive rats among di-peptides of VY, Ile-Tyr, and Tyr-Val irrespective of their angiotensin I-converting enzyme inhibitory activity. The effect was endothelium-independent, and was closely associated with vascular responses in the vascular smooth muscle layer.

DOI： 10.1271/bbb.60119

Language：Japanese   Publishing type：Research paper (scientific journal)  

Language：Japanese   Publishing type：Research paper (scientific journal)  

Production of 6-O-Caffeolysophorose of acylated anthocyanins from puple sweet potato by weak acid hydrolysis

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.2116/analsci.21.997

Language：Japanese   Publishing type：Research paper (scientific journal)  

Antihypertensive effect of Mirin, a fermented traditional product, in SHRs

Language：Japanese   Publishing type：Research paper (scientific journal)  

Isolation of ACE inhibitory peptides from Mirin, a fermented traditional product

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1021/jf047906z

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1271/bbb.68.2239

Language：English   Publishing type：Research paper (scientific journal)  

We hydrolyzed pearl oyster meat with alkaline protease treatment. We administered orally hydrolysate of pearl oyster meat to 8 week-old male SHR/Izm. As a result, the systolic blood pressure of SHR fell significantly from our last quotation of 202.4 mmHg to 180.0 mmHg in six hours. We controlled, isolated and identified four kinds of physiologically active peptides with low molecular weight and high level of ACE inhibition, and refined and identified them as Phe-Tyr, Ala-Trp, Val-Trp, and Gly-Trp with reversed phase chromatography. Among them, Ala-Trp was new and naturally occurring peptide. We estimated that the percentage contributing to ACE inhibition by those four peptides is 4.5%. Based on the study, we believe that promote pearl oyster meat as nutritious and functional food reduces blood pressure.

Language：English   Publishing type：Research paper (scientific journal)  

The quantification of glucose by using a multi-channel dissolved oxygen (DO) meter (DOX96) with immobilized glucose oxidase (GOD) and mutarotase (MUT) was performed. An evaluation of the inhibitory activities for α-glucosidase (AGH) by modifying our batch-type pseudo-in vivo assay system [Oki et al.; Biol. Pharm. Bull., 2000, 232, 1084] was also performed using a DOX96. When 45 U/well GOD and 18.75 U/well MUT were immobilized on the surface of a gelatin membrane on the electrodes, the response shown by the decrease percent of DO (%) obtained with 8 electrode wells in the same row was linear with the glucose concentration up to 3.3 mM and a correlation coefficient larger than 0.9. To estimate the AGH inhibitory activity, AGH-immobilized Sepharose supports in the well of a silent screen plate were used. The IC50 values of acarbose and 1-deoxynojirimycin, a medicinal inhibitor for diabetes, were 0.70 ± 0.08 μM and 0.40 ± 0.13 μM, respectively, and coincided well with those by a pseudo-in vivo assay.

Language：Japanese   Publishing type：Research paper (scientific journal)  

A randomized double-blind placebo-controlled study was conducted on 63 subjects to determine the antihypertensive effect of a vegetable drink in which sardine protein hydrolysates containing a dipeptide, Valyl-Tyrosine (VY), were incorporated. The subjects, consisting of people with mild hypertension, high-normal blood pressure and normal blood pressure, were randomly divided into test (male/female = 25/6, average age 50.1 +/- 10.4 years old) and control groups (26/6, 49.0 +/- 5.0). Each subject in the test group was given 195 g of the vegetable drink containing 0.5 g of sardine peptides (sardine protein hydrolysates) with 0.4 mg of VY (test drink) once a day for 13 weeks in a row, and subjects in the control group were given the same amount of the vegetable drink without sardine peptides (control drink) in the same manner. In the test group, 40 subjects with mild hypertension or high-normal blood pressure (130 mmHg < or = systolic blood pressure (SBP) < 160 mmHg and/or 80 mmHg < or = diastolic blood pressure (DBP) < 100 mmHg) showed a significant decrease in SBP, from 142.0 +/- 10.3 mmHg at the start of the test to 134.4 +/- 11.1 mmHg during the first week of the test period, after which similar values were seen throughout the test period (13 weeks). Compared to the control group, the difference in SBP from baseline was statistically significant in the test group throughout the intake period. DBP also decreased significantly from 88.0 +/- 7.9 mmHg at baseline to 83.5 +/- 8.6 mmHg after 13 weeks. In the control group, SBP and DBP were 140.8 +/- 8.4 mmHg and 90.5 +/- 6.6 mmHg respectively at the start of the test, and neither decreased during the test period. In subjects with normal blood pressure, neither those in the test group nor those in the control group showed a significant change in SBP and DBP during the test period. An excessive ingestion test was performed on 25 subjects with hypertension, mild hypertension, high-normal blood pressure, and normal blood pressure by giving 585 g (3 times the recommended amount of intake) of the test drink for 14 days in a row. As a result, a significant decrease of blood pressure was observed in the hypertension, mild hypertension and high-normal blood pressure groups, but no excessive decline in blood pressure or any side-effects were associated with any subjects during the test period. In the groups with normal blood pressure, the excessive ingestion of the test drink did not affect blood pressure. In these two studies, physical check-ups and biochemical analyses of blood and urine were also conducted in all subjects, and no abnormalities were observed. These results suggest that the test drink containing sardine protein hydrolysates exhibited the antihypertensive effect in only the subjects with mild hypertension or high-normal blood pressure. No adverse effects were observed in either hypertensive or normotensive subjects.

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.2116/analsci.18.467

Language：English   Publishing type：Research paper (scientific journal)  

In order to clarify the postprandial glucose suppression via α-glucosidase (AGH) inhibitory action by natural compounds, flavonoids were examined in this study. Among the flavonoids (luteolin, kaempferol, chrysin, and galangin), luteolin showed the potent maltase inhibitory activity with the IC₅₀ of 2.3 mM, while less inhibitions were observed against sucrase. In addition, the effects of maltase inhibition by flavonoids were observed in the descending order of potency of luteolin >kaempferol >chrysin >galangin. Apparently, the AGH inhibition power greatly increased with the replacement of hydroxyl groups at 3′ and 4′-position of the B-ring. However, the inhibitory power of luteolin was poorer than a therapeutic drug (acarbose: IC₅₀; 430 nM). As a result of a single oral administration of maltose or sucrose (2 g/kg) in SD rats, no significant change in blood glucose level with the doses of 100 and 200 mg/kg of luteolin was observed. These findings strongly suggested that luteolin given at less than 200 mg/kg did not possess the ability to suppress the glucose production from carbohydrates through the inhibition of AGH action in the gut.

Language：English   Publishing type：Research paper (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)  

Language：Japanese   Publishing type：Research paper (scientific journal)  

Preparation and isolation of angiotensin I-converting enzyme inhibitory substrates from chiken essence hydrolysate.

Language：English   Publishing type：Research paper (scientific journal)  

We report here the isolation of α-glucosidase (AGH) inhibitory peptides derived from sardine muscle hydrolyzate, which was prepared by digestion with Bacillus licheniformis alkaline protease. As a result of reversed-phase HPLC purification, two AGH inhibitory peptides were isolated from a DEAE-Sephadex A-25 column eluate. The peptides were identified as follows: Val-Trp (IC₅₀ = 22.6 mM) and Try-Tyr-Pro-Leu (IC₅₀ ± 3.7 mM). AGH inhibitory studies of Try-Tyr-Pro-Leu and its derivatives demonstrated the importance of the tripeptide chain length as well as the hydrophobic aromatic amino acid tyrosine at the N-terminus, aliphatic amino acids at the C-terminus, as well as an amide proton from the peptide chain at the middle position of the tri-peptide to develop AGH inhibition activity.

Language：English   Publishing type：Research paper (scientific journal)  

A variety of glutaraldehyde (GA) activated-aminopropyl controlled pore glass supports were prepared in lower protogenic solvents (methanol, ethanol, and n-propanol). When trypsin was used as the ligand, the amount of trypsin immobilized on them decreased in the order of water, methanol, ethanol, and n-propanol; the maximal reduction of 22% was observed in n-propanol versus that in water. The Michaelis constants of the trypsins immobilized on the support activated with GA in alcohols, especially ethanol and propanol, were smaller than that in water, and the minimum Km value of 1.84X10^-1 mM was obtained in propanol (4.29X10^-1 mM in water). During the reaction of GA with 2-aminoethanol, the amount of the aldehyde group from GA being capable of reacting with 2-aminoethanol significantly decreased when the reaction was done in n-propanol (0.18 mmol/assay volume, cf. in water; 035 mmol/assay volume). The gel permeation chromatography (GPC) measurement of the GA complex, glycine-GA-phenetylamine, also revealed the suppression of the GA self-polymerization in the lower protogenic alcohol as a support activating solvent.

DOI： 10.3136/fstr.5.13

Language：English   Publishing type：Research paper (scientific journal)  

Eight new anthocyanins 1-8 (ternatins C1, C2, C3, C4, C5, and D3 and preternatins A3 and C4) were isolated from Clitoria ternatea flowers. By the application of chemical, UV-vis, and FABMS methods, the structures of 1-6 were postulated as delphinidin 3-malonylglucoside having 3'-GCGC-5'-G, 3'- GCGCG-5'-G, 3'-GC-5'-G, 3'-GCG-5'-G, 3'-G-5'-G, and 3'-GC-5'-GC, and compounds 7 and 8 as delphinidin 3-glucoside having 3'-GCG-5'-GCG and 3'- GCG-5'-G as side chains, respectively, in which Dp is delphinidin, G is D- glucose, and C is p-coumaric acid. The structures of the compounds 1, 3-5, and 7 were established completely by additional NMR methods.

DOI： 10.1021/np980160c

Language：English   Publishing type：Research paper (scientific journal)  

In order to remove oxygen from food packaging, disodium ascorbic acid/polyvinyl chloride (AsN/PVC) was coated onto its cap. When a container with a AsN/PVC cap containing 100 mg of AsN was used for a storage experiment, the oxygen in it was effectively removed more than 50% from the headspace during 30 days' storage at 35°C. The consumption behavior of oxygen was found to depend on the headspace volume of the container; for the container with 31 ml of headspace volume the O ₂ consumption ratio per volume was 1.4-fold higher than that for the container with 77.5 ml of the volume. Also, the O ₂ consumption lowered with lower storage temperature. By using the AsN/PVC cap, flavors in the container were successfully preserved from the oxidative deterioration; the residual ratios for n-hexanal, n-heptanal, d-limonene, and α-pinene with the AsN/PVC cap were 65.0%, 48.9%. 39.1% and 41.0%, respectively after 42 days' storage. In addition, when the cap was used for a liquid food container with 46.5 ml of headspace volume, more than 85% of dissolved oxygen was found to be removed from 0.1% arabic gum solution within 25 days' storage.

Language：English   Publishing type：Research paper (scientific journal)  

An investigation was made of the enzymatic hydrolysis of ovalbumin (OVA), a major allergen in egg white, by various acid and alkaline proteases. Protease YP-SS (acid protease) from Aspergillus niger and alcalase (alkaline protease) from Bacillus licheniformis were found to be useful for the degradation of OVA, respectively. OVA was almost totally hydrolyzed within 15 hr at 37°C by alcalase. Alcalase acted rapidly to hydrolyze OVA, with about 90% of OVA being hydrolyzed within 30 min., the reaction then proceeded more slowly. The antigenicity of the OVA hydrolysate was investigated with IgG raised in rats against OVA and it was apparent that the antigenicity had been almost completely destroyed.

Language：English   Publishing type：Research paper (scientific journal)  

An in vitro degradation test of angiotensin (ANG) II or III in normotensive supine human plasma from 9 healthy male subjects confirmed the production of smaller ANG metabolites with angiotensin I-converting enzyme inhibitory activity. These metabolites were identified as ANG (3–8), ANG (4–8), ANG (5–8), and ANG (3–4), whose respective peptide concentrations were determined by our proposed naphthalene-2, 3-dialdehyde (NDA)-HPLC method to be 64 ±9, 39 ±5, 176 ± 22, and 197 ± 35 fmol/ml of plasma. Pediococcus sp. ISK-1 isolated in our laboratory from well-aged Nukadoko, produces a bacteriocin which has a unique antimicrobial spectrum among pediocins. The bacteriocin was stable at acidic pH, and more than 60% of the antimicrobial activity still remained even after being autoclaved at 121°C for 20min in the pH range of 3 to 8. This is the first report dealing with a bacteriocin produced by lactic acid bacteria isolated from Nukadoko.

DOI： 10.1271/bbb.61.1052

Language：English   Publishing type：Research paper (scientific journal)  

A glutaraldehyde (GA) spacer complex on enzyme immobilization was cleaved from the support introduced N^α -9-fluorenylmethyl-oxycarbonylglycine. By the ¹H-NMR spectroscopic measurement of the desired complex, glycine-GA-phenethylamine (GGP), GA was thought to be involved in enzyme immobilization as a heteropolymer with the molecular weight range of about 600 to 1300.

DOI： 10.1271/bbb.61.893

Language：English   Publishing type：Research paper (scientific journal)  

The effect of activating the renin-angiotensin system on the metabolism of angiotensins (ANGs) in normotensive human plasma was investigated. In normotensive supine human plasma, four peptides with in vitro angiotensin I-converting enzyme (ACE) inhibitory activity which correspond to the sequence of ANG (3–8), ANG (4–8), ANG (5–8), and ANG (3–4) existed at a concentration of > 39fmol/ml of plasma. When activating the renin activity by keeping upright in posture for 60min, ANG II and the four peptides significantly increased as compared with the levels in the supine posture, except for ANG I. In particular, Val-Tyr corresponding to ANG (3–4) in the upright posture was about 4-fold more than the value in the supine posture, and was predominantly present (447 fmol/ml of plasma) as well as ANG I. As a result of in vitro degradation tests on ANGs, ANG (3–4) was produced from ANG I, and not from ANG II, III or (3–8), during the 30-min incubation.

DOI： 10.1271/bbb.61.1814

Language：Japanese   Publishing type：Research paper (scientific journal)  

Bradykinin was converted rapidly into the fragment 1-8 by kininase I when incubated with human plasma. Kininase II inactivated bradykinin by splitting the Pro⁷-Phe⁸ and the Phe⁵-Ser⁶ bonds in it. ACE inhibitory peptide Val-Tyr and captopril did not inhibit the conversion of bradykinin in human plasma into the fragments 1-8, 1-7 and 1-5. Bradykinin was converted into the fragments 1-7 and 1-5 by dipeptidyl peptidase activity of ACE. Captopril inhibited degradation of bradykinin by dipeptidyl peptidase activity of ACE, but Val-Tyr did not inhibit.

Language：Japanese   Publishing type：Research paper (scientific journal)  

The short chain peptides derived from sardines were incubated for 120 min with an extract of porcine small intestinal mucosa. Digestion-resistant dipeptides found in the digest, Val-Tyr, Val-Trp, Ile-Tyr and Ile-Trp, inhibited angiotensin I converting enzyme (ACE). Amounts of the four dipeptides isolated from the digest using a Sep-pak C-18 cartridge column and three steps of high-performance liquid chromatography, were 85.88, 21.87, 10.69 and 6.51 mg/100 g peptides, respectively, and the contribution of four peptides to total ACE inhibitory activity was 10.5%. It was confirmed that ACE inhibitory dipeptides were present in the digest of the short chain peptides.

DOI： 10.3136/nskkk.43.967

Language：Japanese   Publishing type：Research paper (scientific journal)  

Twelve kinds of food proteins were hydrolyzed by Bacillus licheniformis alkaline proteases to form peptides of average chain length, 2.26-4.02. The hydrolyzates from shrimp, crab and sardine contained many di- and tri-residues whose angiotensin I converting enzyme (ACE) inhibitory activities were stronger than that of the hydrolyzates from soy bean, hair tail, oyster, beef, chicken, pork, chicken egg yolk, chicken egg white and casein. The IC₅₀ was 0.072, 0.075 and 0.076 mg protein/ml, respectively. Hydrophobic amino acid residues situated in the interior of protein molecules were exposed by fragmentation with proteases, and the peptides containing hydrophobic amino acid residues were found in aqueous solution. The peptide from casein showed the highest hydrophobicity and whose taste was the most bitter.

DOI： 10.3136/nskkk.43.839

Language：Japanese   Publishing type：Research paper (scientific journal)  

The peptides with average molecular weight 315 were prepared from sardine proteins by Bacillus licheniformis alkaline proteases. The short chain peptides had no bitter taste and little fish flavor. The short chain peptides showed the potent angiotensin I-converting enzyme (ACE) inhibitory activity, which was high resistance to the hydrolysis by any digestive proteases. ACE inhibitory activity of short chain peptides didn't change by the pig intestinal fluid after pepsin digestion. Compared with the long chain peptides in sardine muscle hydrolyzate prepared by digestive proteases, inhibitory activities of various digest were weaker than that of the short chain peptides derived from alkaline proteases hydrolyzate. The short chain peptides were assayed in spontaneously hypertensive rats and found to reduce on blood pressure.

DOI： 10.3136/nskkk.43.520

Language：Japanese   Publishing type：Research paper (scientific journal)  

In order to remove dissolved oxygen from liquid food, ascorbate oxidase (AO) was covalently immobilized onto ethylene-vinyl alcohol copolymer (EVOH) film. Maximal activity was observed at pH 6.0, 30°C (1.14 mU/cm²). The immobilized AO still retained a higher residual activity than free AO under practical conditions ; at pH 4.0 corresponding to citrus juice, 10°C and 60°C, the residual activities were 47.8%, 91.3%, and 49.4% whereas those of free AO were 3.1%, 63.3% and 0%, respectively. When the AO immobilized EVOH film was directly in contact with 2.5 mM L-ascorbic acid in 10 mM citrate buffer solution (pH 4.0), more than 85% of dissolved oxygen was removed within 4h. In addition, flavors (d-limonene, linalool, and citral) in the solution were successfully preserved from the oxidative deteriorations ; for d-limonene, the residual ratio (71.6%) with AO immobilized EVOH film was 2.5-fold that with non-immobilized one (29.0%) after 28 days' storage.

DOI： 10.3136/nskkk.43.362

Language：English   Publishing type：Research paper (scientific journal)  

Five new ternatins 1-5 have been isolated from Clitoria ternatea flowers, and the structures have been determined by chemical and spectroscopic methods as delphinidin 3-malonylG having 3'-GCG-5'-GCG, 3'- GCG-5'-GC, 3'-GCGCG-5'-GC, 3'-GCGC-5'-GCG, and 3'-GCGC-5'-GC side chains, respectively, in which G is p-glucose and C is p-coumaric acid. Pigment 1 had symmetric 3',5'-side chains. Compounds 3 and 4 are structural isomers. These ternatins were shown to form an intramolecular stacking between the aglycon ring and the 3',5'-side chains in solution.

DOI： 10.1021/np960050a

Language：English   Publishing type：Research paper (scientific journal)  

A survey of food components with α-glucosidase (AGH) inhibitory activity was conducted to identify a prophylactic effect for diabetes in food. Sardine muscle hydrolyzed by alkaline protease showed potent activity (IC₅₀ = 48.7mg/ml) as well as green and oolong teas (IC₅₀ = 11.1 and 11.3mg/ml, respectively). Furthermore, hydrolyzates prepared by various proteases gave differing AGH inhibitory activity. DEAE-Sephadex chromatography of the alkaline protease hydrolyzate eluted potent AGH inhibitors (IC₅₀ = 15.6mg/ml) with a 50 mM phosphate buffer (pH 7.0) containing 0.3 m NaCl, and their subsequent separation by HPLC in an ODS column showed that there were some inhibitors possessing primary amino groups. This indicates that they would have been high anionic and peptidic compounds.

DOI： 10.1271/bbb.60.2019

Language：Japanese   Publishing type：Research paper (scientific journal)  

Peptide hydrolases were prepared from porcine small intestinal mucosa and their properties were examined using the following peptide substrates : Arg-Lys-Glu-Val-Tyr, Arg-Lys-Asp-Val-Tyr, Val-Tyr-Val, ACE inhibitory dipeptides, and other dipeptides. Peptide hydrolases hydrolyzed all the peptides above cited, and released the amino acid from the NH₂-terminus of the tri and pentapeptides. Ile-His, Gly-Pro, Phe-Pro, His-Pro, Pro-Phe, Asp-Glu, Asp-Asp, Glu-Glu, Glu-Asp, Gly-Sar, Pro-Gly, and Val-Tyr showed resistance to dipeptidases, but, Gly-Trp, Met-Phe, and Arg-Tyr, with ACE inhibitory activity were rapidly hydrolyzed. Glu-Val-Tyr and Asp-Val-Tyr rapidly released Glu and Asp, respectively, as tri and aminopeptidases. The results suggested that the primary structure of dipeptides, tripeptides, and oligopeptides are involved in ACE activity. Val-Tyr is a major ACE inhibitory peptide derived from sardines. Also, oligopeptides having Val-Tyr at the COOH-terminus were rapidly hydrolyzed by peptide hydrolases including tri and aminopeptidases from porcine small intestinal mucosa, but, resistant Val-Tyr had a potent ACE inhibitory activity.

Language：Japanese   Publishing type：Research paper (scientific journal)  

Short chain peptides with the average chain length of 2.67 prepared from sardine protein have reductive effects on blood pressure, and are expected to be a physiologically functional foodstuff. The short chain peptides were found to be negative in the active systemic anaphylaxis (ASA) test in guinea pigs sensitized by oral administrations of the short chain peptides. Negative results were also obtained in the homologous passive cutaneous anaphylaxis (PCA) test, which was done against sera from guinea pigs sensitized by oral administration of the short chain peptides. The short chain peptides have a potent angiotensin I converting enzyme (ACE) inhibitory activity, this enzyme catalyses the activation of angijotensin II and inactivation of bradykinin. The bradykinin is able to stimulate macrophages, to enhance lymphocyte migration, and to increase secretion of lymphokines. The short chain peptides favor bradykinin activity, which showed concentrated pigment coloration in the PCA test by subcutaneous sensitization. These results suggest that the short chain peptides have no antigenicity by oral administration, and are usable in foods.

DOI： 10.1271/nogeikagaku1924.69.1171

Language：Japanese   Publishing type：Research paper (scientific journal)  

The NH₂-terminal residue of a dipeptide is an important determinant of the resistance to peptidases of porcine small mucosa. NH₂-terminal Val or Ile, and COOH-terminal Trp or Tyr dipeptides had higher angiotensin I converting enzyme(ACE)inhibitory activity and digestive resistance than other dipeptides. We defined Val-Tyr as a main inhibitor in alkaline protease hydrolyzates from sardines. Attempts to isolate and measurement of Val-Tyr were done from the short chain peptides that reduced blood pressure. The content of Val-Tyr was 51 mg per 100 g of the short chain peptides, represented 1.3% of the total ACE inhibitory activity of the short chain peptides. Isolated Val-Tyr was resistant to gastrointestinal proteases. The primary structures of fragments formed from Arg-Val-Tyr by digestive proteases were considerably different, and it was confirmed that the main peptide, Val-Tyr, was formed by intestinal proteases after digestion. The content of Val-Tyr formed from the short chain peptides by intestinal proteases after digestion was less than 10 percent of the original.

DOI： 10.1271/nogeikagaku1924.69.1013

Language：English   Publishing type：Research paper (scientific journal)  

When angiotensin fragments, Val-Tyr and Angiotensin III (ANG III), with potent ACE inhibitory activity were intravenously administered to spontaneously hypertensive rat (SHR), a significant reduction of diastolic blood pressure was observed. After incubation of ANG III with SHR plasma, four fragments with ACE inhibitory activity, Val-Tyr (ANG (3-4)) (IC₅₀=26.0μM), Ile-His-Pro-Phe (ANG (5-8)) (11.6μM), Tyr-Ile-His-Pro-Phe (ANG (4-8)) (457.5μM), and Val-Tyr-Ile-His-Pro-Phe (ANG (3-8)) (6.55μM), were confirmed to generate in SHR plasma. Compared the metabolic behavior of ANG II in SHR plasma with that in normotensive Wistar plasma, the initial degradation rate (3.07nmol/ml/min) in Wistar plasma was about 2-fold higher than that in the SHR one (1.75nmol/ml/min).

DOI： 10.1271/bbb.59.1398

Language：English   Publishing type：Research paper (scientific journal)  

The sorption equation of flavors with packaging film to extend for various flavors and polymers was derived by improving the proposed δ_c concept. On the basis of the findings that the sorptions depend on both the δ_c values between film and flavors with similar chemical potential and their molar heat of vaporization (ΔH_vap), the following thermodynamic sorption equation was derived: S = S_o exp γ[V_v(δ_v²-δ_c²)/RT]. For aqueous phase the plots of In S vs the term of the equation gave an adequate but insufficient relationship (r = 0.802), resulting from the influence of any interaction force from solution on the magnitudes of physical adsorption and condensation of flavors on film surface. On the other hand, for vapor phase the same plots gave a quite sufficient correlation (r = 0.967). Therefore, in the prediction of the sorption behaviors for vapor phase the derived sorption equation may be more useful and effective.

DOI： 10.1021/jf00048a045

Language：English   Publishing type：Research paper (scientific journal)  

A further approach to derive the thermodynamic sorption equation for aqueous phase was performed by estimating the molar heat of sorption (ΔH_s) accurately. On the basis of the findings that the sorption of a volatile compound depends on both its molar heat of mixing into film and its enthalpy change toward film, the following equation could be successfully derived: S = S₀ exp γ, [V_v[(δ_w-δ_v)² —, δ_c²]/RT]. The plots of In S into LDPE film vs the term of the equation gave more adequate improvement in the correlation (r = 0.968). Taking into account the volatility (α) of a volatile compound from solution, further improvement of the equation was made: S = α, S₀ exp γ, [V_v[(δ_w-δ_v)² —, δ_c²]/RT]. The plots of In S/α, vs the term of the equation for both sugar-ester and SDS solutions gave a sufficient correlation (r = 0.959). Furthermore, the equation could be sufficiently applied to various polymers (PP, r = 0.931, EVA, r = 0.963, EVOH, r = 0.932).

DOI： 10.1021/jf00048a046

Language：English   Publishing type：Research paper (scientific journal)  

Surface cross-linking treatment of ethylene—vinyl acetate copolymer (EVA) film was performed by formalization in a moderate condition. This treatment led to a marked depression of flavor sorptions. Maximal sorption depression was observed for 18.8 mmol % formalized film, and the maximal depression ratio of solubility coefficient against the unformalized one was about 54% for decane. To elucidate this phenomenon, sorption depression ratios against molecular size were plotted. The sorption of flavors was linearly depressed with an increase in the molecular sizes of the compounds, and the plots for ethyl esters, aldehydes, and alcohols were on the same line (r = 0.842). According to the SEM analysis, which revealed the formation of cross-linkage in the formalized film, the depression effect may be attributed to a restriction of the chain mobility in amorphous regions.

DOI： 10.1021/jf00045a029

Language：English   Publishing type：Research paper (scientific journal)  

The formation of a βCD inclusion complexfor aliphatic ethyl ester, with ethyl hexanoateas a guest molecule was investigated. Proton T₁ measurements by the IR method and ID difference nuclear Overhauser enhancement experiments showed that ethyl hexanoate exists with the groups (H-2 and H-3) around the ester bond nearer to the narrower βCD cavity and the other protons are proximal to the H(CD)-3 and H(CD)-5 protons within the cavity with a folded structure. The complexation of βCDwas greatly affected by the addition of ethanol. With increasing ethanol concentration, a marked increase in volatility of ethyl hexanoate from the βCD solution was observed; the volatility in 30% ethanol was about 3 times larger than in 0% one. On the basis of the observed NOE and T₁ values, the lowering of the abilityof PCD complexation in ethanol solution is assumed to be caused by the situation shift of guest molecule toward the narrower side or outside of the cavity.

DOI： 10.1271/bbb.58.1102

Language：English   Publishing type：Research paper (scientific journal)  

Surface hydrolysis of ethylene-vinyl acetate copolymer (EVA) film resulted in a specific sorption depression behavior of volatile compounds. The sorptions of hydrocarbons, ethyl octanoate, and decanal into hydrolyzed EVA film were depressed, whereas the sorptions for alcohols were all promoted. To elucidate the phenomena, the solubility parameter (SP) concept was introduced. From the plots of sorptions against the SP values of volatile compounds, for all hydrocarbons, ethyl esters, and aldehydes with the cohesive energy of <19.3 SP value, the sorptions were depressed, while for hexanal and all alcohols with the SP value of >19.3 quite the opposite results were obtained. It was considered that the depression effect may be attributed to the lowering of compatibility at the surface between hydrolyzed film and volatile compounds. Sensory evaluation also supported flavor preservation for hydrolyzed EVA film in lemon juice.

DOI： 10.1021/jf00030a018

Language：English   Publishing type：Research paper (scientific journal)  

In order to estimate the sorption behaviors of flavors into film packaging, a two-dimensional approach based on the affinity of flavor for film was performed. When the solubility parameter (SP) value is divided into polar and nonpolar components, the affinity can be represented as a two-dimensional distance (δ_c) between two SP values of film and flavor. On the basis of this δ_c concept, the sorptions of flavors into MDPE and EVOH films in the aqueous phase were proved to depend on the δ_c value; the logarithms of the solubility coefficient decreased linearly with an increase in δ_c value, i.e., about one-sixth decrease for one δ_c value. In addition, a large negative slope of the line indicated that the sorption was remarkably influenced by affinity (δ_c).

DOI： 10.1021/jf00022a035

Language：English   Publishing type：Research paper (scientific journal)  

Electron beam irradiation of ethylene‐vinyl acetate copolymer (EVA) film results in a marked depression of sorption of flavour compounds. This effect is presumed to be brought about by radical reactions, following changes in the structure. The crosslinking density and gel fraction increased with irradiation dose, and the maximum percent gel reached 70% for 20 Mrad‐50g kg⁻¹ EVA film, 35% for 20 Mrad‐95g kg⁻¹ EVA film and 50% for 10 Mrad‐150g kg⁻¹ EVA film. In calculating the ratio of scission to crosslinking events, it was found that EVA film is a polymer of the scission type. The degree of crystallinity, X_c decreased significantly with increasing irradiation dose in all irradiated films. For unirradiated films, X_c decreased with increase in vinyl acetate content, which suggests that crystalline regions of EVA film are primarily composed of ethylene units. Therefore, the scission reaction may predominantly take place in the crystalline region, resulting in the formation of methyl or end vinyl groups. This was supported by measuring the film density, peak melting temperature and stress at yield.

DOI： 10.1002/pi.4990290204

Language：English   Publishing type：Research paper (scientific journal)  

The crosslinked structure of irradiated ethylene‐vinyl acetate copolymer (EVA) film was examined by means of ESR, IR and pyrolysis‐gas chromatography. The ESR spectrum of 35 Mrad irradiated EVA film with 95g kg⁻¹ vinyl acetate content consisted of a three‐line component with an intensity ratio of 1:2:1, a hyperfine structure coupling of 22.4 G and g factor of 2.0049. Therefore, the spectrum was assigned to the methylene radical with two α protons on the same plane; this radical is formed by loss of a hydrogen atom from the acetoxymethyl group. In pyrolysing EVA films at 500°C, the yield of acetic acid from 10 Mrad‐150 g kg⁻¹ film significantly decreased compared with that of unirradiated film, and it decreased with increasing crosslinking density. By measuring the IR spectra of methanolysed EVA films, the following results were obtained: the absorbances at 1740, 1250 and 1050cm⁻¹, attributed to the CO, OCOR and COC groups, respectively, had a marked decrease, whereas the three peaks for 20Mrad film were much stronger than those of unirradiated film. On the basis of these findings, it is suggested that the crosslinking reaction in electron beam irradiated EVA film with lower doses takes place between the acetoxy groups and the main chains.

DOI： 10.1002/pi.4990290205

Language：English   Publishing type：Research paper (scientific journal)  

Electron beam irradiation for low-density polyethylene (LDPE) film up to 20 Mrad resulted in specific sorption depression behaviors of volatile compounds. The sorptions of octane, ethyl hexanoate, and d-limonene into irradiated film were depressed, whereas the opposite behavior was obtained for octanal and octanol. To elucidate these specific phenomena, a thermodynamic attempt of applying the solubility parameter (SP) value was done. As a result, the sorptions of all hydrocarbons and methyl and ethyl esters composed of more than six carbon atoms corresponding to <8.59 SP value were depressed in all, while sorption promotion was observed for all alcohols. A similar result was obtained for irradiated EVA film, for which the sorption depression was observed only for the volatile compound with <8.93 SP value. Calculating the ratio of SP value of volatile compound (δ_F) to that of irradiated film (δ_P), the ratios (δ_F/δ_P) for irradiated LDPE and EVA films gave good agreement at 1.09.

DOI： 10.1021/jf00015a024

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1271/bbb.56.517

Language：English   Publishing type：Research paper (scientific journal)  

Three peptides that inhibited angiotensin I converting enzyme (ACE) were isolated from a peptic hydrolyzate of heated sardine muscle. The preparation involved SP-Sephadex C-25 and Toyopearl HW-40 chromatography followed by three steps of high-performance liquid chromatography. The amino acid sequences of these peptides, identified by Edman degradation, were: values of these peptides for ACE from rabbit lung were 83, 30, and 188 μM, respectively. These peptides were synthesized by the solid-phase method, and the IC₅₀ values of the synthetic peptides were similar to those of B-1, B-2, and B-3. These results indicated that all amino acids in B-1, B-2, and B-3 may be in the L-configuration. Fourteen kinds of actins derived from humans, rabbits, rats, mice, soy beans, maize, and so on contained the B-1 sequence of five amino acids.

DOI： 10.1271/nogeikagaku1924.66.25

Language：English   Publishing type：Research paper (scientific journal)  

In order to investigate the sorption of volatile compounds by electron beam irradiated ethylene/vinyl acetate copolymer (EVA) films, permeation measurements in the vapour phase were carried out. The diffusion coefficients of octane, ethyl hexanoate, octanal, octan‐1‐ol and d‐limonene increased with an increase in the irradiation dose. The sorption of all volatile compounds in this study was depressed in electron beam irradiated film: the decreases in solubility coefficients for 20 Mrad EVA film were 15% for octane and ethyl hexanoate, 45% for octan‐1‐ol and octanal, and 50% for d‐limonene. The enthalpy change in sorption (ΔH) of ethyl hexanoate was −13·4 kJ mol⁻¹ for 50 g kg⁻¹ EVA film at a dose of 20 Mrad compared with −27·6 kJ mol⁻¹ for the unirradiated one. In a homologous series of aliphatic alcohols, sorption was significantly depressed with increasing carbon chain length. Judging from both heat‐seal strength and sorption behaviours, the most appropriate irradiation dose for the practical usage of irradiated EVA film was less than 15, 10 and 5 Mrad for 50, 95 and 150 g kg⁻¹ EVA film, respectively.

DOI： 10.1002/jsfa.2740540114

Language：English   Publishing type：Research paper (scientific journal)  

Decrease in solubility of volatile compounds (octan‐l‐ol, octanal, ethyl hexanoate, octane and d‐limonene) into a film liner was studied after electron beam irradiation up to 20 Mrad of ethylene vinyl acetate copolymer (EVA) film. The solubility coefficient decreased gradually during ageing despite no change immediately after the irradiation. In all films dosed with 5‐20 Mrad the sorption was depressed about 40% in comparison with the unirradiated one after 4 months. The behaviour was consistent with that of the decay of the radicals in the films. The enthalpy change in sorption (ΔH) was −18.0 kJ mol⁻¹ for 5 Mrad ethylene vinyl acetate copolymer film compared with −48.1 kJ mol⁻¹ for the unirradiated one. In a homologous series, sorption was significantly depressed with increasing carbon chain length of the volatile compound. The specific sorption depression effect was observed for low polarity compounds such as hydrocarbons, aliphatic esters and d‐limonene. The diffusion coefficient of the sorbed compounds increased about 1.6 times after 3 months when irradiated to 20 Mrad.

DOI： 10.1002/jsfa.2740500409

Total pages：253   Responsible for pages：pp.101-110   Language：Japanese   Book type：Scholarly book

Total pages：333   Responsible for pages：pp.14-23   Language：Japanese   Book type：Scholarly book

Responsible for pages：ペプチド機能と味（第7章、P.129-136）   Language：Japanese   Book type：Scholarly book

Responsible for pages：pp.255-274   Language：English   Book type：Scholarly book

Responsible for pages：第5章   Language：Japanese   Book type：Scholarly book

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Total pages：316   Responsible for pages：低分子・オリゴペプチド（第III編第2章）   Language：Japanese   Book type：Scholarly book

Responsible for pages：匂い成分の合成樹脂への収着・移香の項   Language：Japanese   Book type：Scholarly book

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Responsible for pages：pp.43-54   Language：English   Book type：Scholarly book

Responsible for pages：第5章、pp.213-217   Language：Japanese   Book type：Scholarly book

Responsible for pages：機能性評価実験法-酵素活性制御機能   Language：Japanese   Book type：Scholarly book

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Responsible for pages：第13章　タンパク質とペプチド・アミノ酸の機能性   Language：Japanese   Book type：Scholarly book

Responsible for pages：Anthocyanins as food factor   Language：English   Book type：Scholarly book

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Responsible for pages：第5章（食品ペプチドの血圧低下機構）p.59-70   Language：Japanese   Book type：Scholarly book

Responsible for pages：Bioactive Peptides with Antihypertensive Potency Derived from Natural Protein pp.113-122   Language：English   Book type：Scholarly book

Responsible for pages：食品機能の挑戦−高血圧疾病予防を図る−　pp.33-44   Language：Japanese   Book type：Scholarly book

Food Function-antihypertensive effect of food compounds.

Language：Japanese  

CiNii Books

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CiNii Books

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CiNii Books

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Responsible for pages：209-228   Language：English   Book type：Scholarly book

Prediabetes, typically defined as impaired glucose tolerance, is a high-risk state of developing diabetes. Although there have considerable scientific progresses in related areas, the extended research concerning antidiabetic action of natural compounds at prediabetic stage has been limited due to the lack of specific biomarkers that enable to identify prediabetes state and elucidate the complicated mechanism of antidiabetic action of natural compounds. The increased formation and accumulation of advanced glycation end products (AGEs) have been confirmed as a vital risk of developing hyperglycemia, type 2 diabetes, and diabetic complications. Many researches revealed that AGEs have showed great potential to be served as biomarkers to predict prediabetic condition. The present chapter is aimed to offer an overview of prediabetes and the current research outcomes involved with functionally natural compounds in decreasing the risk of developing diabetes at prediabetic stage.

DOI： 10.1016/B978-0-12-809450-1.00007-7

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Food Analysis

Responsible for pages：Chapter 15 (Antihypertensive Peptides from Natural Resources), pp.259-276 Edited by M.T.H.Khan and A.Ather   Language：English   Book type：Scholarly book

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Venue：長崎大学（長崎）   Country：Japan  

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Venue：長崎大学（長崎）   Country：Japan  

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Venue：長崎大学（長崎）   Country：Japan  

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Venue：名城大学（名古屋市）   Country：Japan