Nobuo Uotsu

Tokyo University of Agriculture and Technology, Tokyo, Tokyo-to, Japan

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Publications (9)14.49 Total impact

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    ABSTRACT: The senescence accelerated mouse prone 8 substrain (SAM-P8), widely accepted as an animal model for studying aging and antiaging drugs, was used to examine the effects of dietary supplementation with extracts of Cistanche deserticola (ECD) which has been used extensively in traditional Chinese medicine because of its perceived ability to promote immune function in the elderly. Eight-month-old male SAM-P8 mice were treated with ECD by daily oral administrations for 4 weeks. The results showed that dietary supplementation of 150 mg/kg and 450 mg/kg of ECD could extend the life span measured by Kaplan-Meier survival analysis in dose-dependent manner. Dietary supplementation of SAM-P8 mice for 4 weeks with 100, 500, and 2500 mg/kg of ECD was shown to result in significant increases in both naive T and natural killer cells in blood and spleen cell populations. In contrast, peripheral memory T cells and proinflammatory cytokine, IL-6 in serum, were substantially decreased in the mice that ingested 100 and 500 mg/kg of ECD daily. Additionally, Sca-1 positive cells, the recognized progenitors of peripheral naive T cells, were restored in parallel. Our results provide clear experimental support for long standing clinical observational studies showing that Cistanche deserticola possesses significant effects in extending life span and suggest this is achieved by antagonizing immunosenescence.
    Evidence-based Complementary and Alternative Medicine 01/2014; 2014:601383. · 1.72 Impact Factor
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    ABSTRACT: Kale (Brassica oleracea L. var acephala DC) is a leafy green vegetable belonging to the cabbage family (Brassicaceae) that contains a large amount of health-promoting phytochemicals. There are any reports about the effects of kale ingestion on the chemoprevention function and mechanism, but the interactions between kale and drugs have not been researched. We investigated the effects of kale intake on cytochrome P450 (CYP) metabolism by using cocktail probe drugs, including midazolam (for CYP3A4), caffeine (for CYP1A2), dextromethorphan (for CYP2D6), tolbutamide (for CYP2C9), omeprazole (for CYP2C19), and chlorzoxazone (for CYP2E1). Cocktail drugs were administered into rats treated with kale and cabbage (2000 mg/kg) for a week. The results showed that kale intake induced a significant increase in plasma levels and the AUC of midazolam, caffeine, and dextromethorphan. In addition, the plasma concentration and AUC of omeprazole tended to increase. Additionally, no almost differences in the mRNA expression levels of CYP enzymes in the liver were observed. In conclusion, kale ingestion was considered to have an inhibitory effect on the activities of CYP3A4, 1A2, 2D6, and 2C19 for a reason competitive inhibition than inhibitory changes in the mRNA expressions.
    Biomedical Research 01/2012; 33(4):235-42. · 1.15 Impact Factor
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    ABSTRACT: The EtOH extract of tarragon Artemisia dracunculus, a perennial herb in the family Asteraceae, was found to potently inhibit α-melanocyte-stimulating hormone (α-MSH) induced melanin production in B16 mouse melanoma cells. Bioassay-guided fractionation led to the isolation of two alkamide compounds, isobutyl (1) and piperidiyl (2) amides of undeca-2E,4E-dien-8,10-dynoic acid. The respective EC(50) values for melanin biosynthesis inhibition were 1.8 and 2.3 µg/mL for 1 and 2.
    Bioscience Biotechnology and Biochemistry 08/2011; 75(8):1628-30. · 1.27 Impact Factor
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    ABSTRACT: Kale is a cruciferous vegetable (Brassicaceae) that contains a large amount of health-promoting phytochemicals. The chronic ingestion of cabbage of the same family is known to accelerate conjugating acetaminophen (AA) and decrease the plasma AA level. Therefore, we examined to clarify the effects of kale on the pharmacokinetics of AA, its glucuronide (AA-G) and sulfate (AA-S). AA was orally administered to rats pre-treated with kale or cabbage (2000 mg/kg/day) for one week. Blood samples were collected from the jugular vein, and the concentrations of AA, AA-G and AA-S were determined. In results, kale ingestion induced an increase in the area under the concentration-time curve (AUC) and a decrease in the clearance of AA, whereas cabbage had almost no influence. In addition, there were significant differences in the AUC of AA-G between the control and kale groups. mRNA expression levels of UDP-glucuronosyltransferases, the enzymes involved in glucuronidation, in the kale group were significantly higher than those in the control group. In conclusion, kale ingestion increased the plasma concentrations of both AA and AA-G. The results suggest that kale ingestion accelerates the glucuronidation of AA, but an increase of plasma AA levels has a different cause than the cause of glucuronidation.
    Biomedical Research 01/2011; 32(6):357-62. · 1.15 Impact Factor
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    ABSTRACT: Difructose anhydride III (DFAIII) is an indigestible disaccharide and has been shown to enhance iron absorption in animal studies; however, the effect has not been investigated in anemic subjects. We investigated the efficacy of co-administration of DFAIII with water-insoluble iron in the treatment of iron deficiency anemia in Vietnamese women. One hundred sixty-eight moderately anemic women (80 g/L<hemoglobin (Hb)<120 g/L) participated in a double-blinded, placebo-controlled study with daily supplementation of iron for 6 mo. The volunteers were randomly assigned into four groups, i.e., Group A: received 15 mg Fe as ferric pyrophosphate; Group B: received 15 mg Fe as ferric pyrophosphate and 1.25 g DFAIII; Group C: received 15 mg Fe as ferrous sulfate; Group D: received a placebo. Hb and iron status were measured at baseline and after 2, 4 and 6 mo of intervention. The ratio of transferrin receptor to ferritin was used to estimate stored and functional body iron (BI). One hundred sixteen (69.0%) women completed the trial. After 6 mo, mean (+/-SE) Hb concentration was higher in Group A (121.6+/-1.7 g/L), Group B (126.4+/-1.5 g/L) and Group C (126.8+/-1.6 g/L) compared to Group D (107.0+/-1.7 g/L, p<0.0001). Mean change in BI was twofold greater in Group B (5.0+/-0.5 mg/kg) than that in Group A (2.5+/-0.6 mg/kg, p=0.008). The percentage of anemia was significantly reduced in Group B (18.8%) compared to Group D (95.8%, p<0.0001) and Group A (39.1%, p=0.033). Co-administration of DFAIII enhances Hb concentration and iron stores more than single administration of water-insoluble iron in anemic Vietnamese women.
    Journal of Nutritional Science and Vitaminology 01/2010; 56(3):191-7. · 0.99 Impact Factor
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    ABSTRACT: An EtOH extract of fruits of Piper longum was found to exhibit a potent inhibitory effect against alpha-melanocyte-stimulating hormone (alpha-MSH)-induced melanin production in B16 mouse melanoma cells. Bioassay-directed fractionation led to the isolation of prenylated phenolic compounds bakuchiol, bavachin, and isobavachalcone. These compounds and the crude extract of the fruits of P. longum may have suppressive effects against pigmentation by melanin in the skin.
    Bioscience Biotechnology and Biochemistry 01/2010; 74(7):1504-6. · 1.27 Impact Factor
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    ABSTRACT: The bacterium Clostridium botulinum type C produces a progenitor toxin (C16S toxin) that binds to O-linked sugar chains terminating with sialic acid on the surface of HT-29 cells prior to internalization [A. Nishikawa, N. Uotsu, H. Arimitsu, J.C. Lee, Y. Miura, Y. Fujinaga, H. Nakada, T. Watanabe, T. Ohyama, Y. Sakano, K. Oguma, Biochem. Biophys. Res. Commun. 319 (2004) 327-333] [21]. Based on this, it was hypothesized that the C16S toxin is internalized via clathrin-coated pits. To examine this possibility, the internalized toxin was observed with a fluorescent antibody using confocal laser-scanning microscopy. The confocal images clearly indicated that the C16S toxin was internalized mainly via clathrin-coated pits and localized in early endosomes. The toxin was colocalized with caveolin-1 which is one of the components of caveolae, however, implying the toxin was also internalized via caveolae. The confocal images also showed that the neurotoxin transported to the endosome was transferred to the Golgi apparatus. However, the non-toxic components were not merged with the Golgi marker protein, TGN38, implying the neurotoxin was dissociated from progenitor toxin in endosomes. These results suggested that the C16S toxin was separated to the neurotoxin and other proteins in endosome and the neurotoxin was further transferred to the Golgi apparatus which is the center for protein sorting.
    Biochimica et Biophysica Acta 02/2006; 1763(1):120-8. · 4.66 Impact Factor
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    ABSTRACT: We found here that マ・epoxyalkyl ホア-D-glucopyranosides consisting of three, four and five alkyl carbons (ホア-E3G, ホア-E4G and ホア-E5G, resp.), which are known to be affinity-labeling reagents of ホイ-amylase, had the effect of inactivating two pullulan-hydrolyzing ホア-amylases from Thermoactinomyces vulgaris R-47, TVA I and TVA II, at high concn. (ca. 0.1-1.5 M). The inactivation exhibited satn. kinetics of a two-step mechanism, and an inactivation rate const., k, and equil. dissocn. const., KR, of ホア-E5G were calcd. The k/KR values of ホア-E5G for TVA I and TVA II were 13.1 テ・10-4 and 6.41 テ・10-4 M-1ツキs-1 resp. In terms of the power of inactivation, the orders for TVA I and TVA II were ホア-E5G > ホア-E3G 竕・ホア-E4G, and ホア-E5G > ホア-E3G > ホア-E4G, resp. The findings indicated that the relation between the lengths of the alkyl carbons and the inactivation of TVA I and TVA II differs from that of ホイ-amylase and isomalto-dextranase. [on SciFinder(R)]
    J. Appl. Glycosci. 01/2005; 52(3):273-276.
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    ABSTRACT: Orally ingested botulinum toxin enters the circulatory system and eventually reaches the peripheral nerves, where it elicits a response of neurological dysfunction. In this study, we report the important findings concerning the mechanism of Clostridium botulinum type C progenitor toxin (C16S) endocytic mechanism. C16S toxin bound to high molecular weight proteins on the surface of human colon carcinoma HT-29 cells and was internalized, but not if the cells were pretreated with neuraminidase. Benzyl-GalNAc which inhibited O-glycosylation of glycoproteins also interfered in the toxin's ability to bind the cell surface. On the other hand, the toxin was internalized in spite of pretreatment of the cells with PPMP, an inhibitor of ganglioside synthesis. These results suggest that the glycoproteins, like mucin, fulfill the important roles of receptor and transporter of C16S toxin.
    Biochemical and Biophysical Research Communications 07/2004; 319(2):327-33. · 2.28 Impact Factor