Hayashikane Sangyo Co.

Shimonoseki, Japan

Hayashikane Sangyo Co.

Shimonoseki, Japan
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Patent
Hayashikane Sangyo Co. | Date: 2016-01-28

A composition and method are disclosed for ameliorating infertility, the composition an extract of one or both of pericarp and fruit of a plant of the genus Trapa, or one or compounds isolated therefrom, as the active ingredient that is safe and has high activity, in which the one or more compounds preferably has an inhibition activity against one or more reactions involving a formation of advanced glycation end products from proteins and saccharides, an enhancing activity against one or more reactions involving a decomposition of the advanced glycation end products and an activity to reduce allergic symptoms.


Suda A.,Kyushu University | Kaiya H.,Japan National Cardiovascular Center Research Institute | Nikaido H.,Seikai National Fisheries Research Institute | Shiozawa S.,Seikai National Fisheries Research Institute | And 3 more authors.
General and Comparative Endocrinology | Year: 2012

Full length cDNA and gene encoding ghrelin precursor and mature ghrelin peptide were identified from the stomach of Pacific bluefin tuna, Thunnus orientalis, which has unique metabolic physiology and high commercial value at fishery markets. Quantitative expression analysis was conducted for the gastric ghrelin and pepsinogen 2 genes during the early stage of somatic growth from the underyearling to yearling fish. The full length cDNA of bluefin tuna ghrelin precursor has a length of 470. bp and the deduced precursor is composed of 107 amino acids. The ghrelin gene is 1.9. kbp in length and has a 4 exon-3 intron structure. The major form of mature ghrelin in the stomach was an octanoylated 20-amino acid peptide with C-terminal amidation, while overall 12 different forms of ghrelin peptides, including short form of 18-amino acid peptide and seven kinds of acyl modifications were identified. The expression profiles of the gastric ghrelin and pepsinogen 2 genes showed no significant changes related to the early growth stages. The present results suggest that digestive physiology has already been functional in this growth stage of the juvenile bluefin tuna and ghrelin may have a role in the sustained digestive and metabolic activities. © 2012 Elsevier Inc.


Shiratsuchi E.,Kyushu Institute of Technology | Ura M.,Kyushu Institute of Technology | Nakaba M.,Hayashikane Sangyo Co. | Maeda I.,Kyushu Institute of Technology | Okamoto K.,Kyushu Institute of Technology
Journal of Peptide Science | Year: 2010

We obtained pure elastin peptides from bovine ligamentum nuchae, porcine aorta, and bonito bulbus arteriosus. The inhibitory activity of these elastin peptides on platelet aggregation induced by collagen and the migratory and proliferative responsivenesses of human skin fibroblasts to these elastin peptides were examined. All of bonito, bovine, and porcine elastin peptides found to inhibit platelet aggregation, but bonito elastin peptides showed a higher inhibitory activity than bovine and porcine elastin peptides did. All elastin peptides enhanced the proliferation of fibroblasts 3.5- to 4.5-fold at a concentration of 10 μg/ml. Bovine and porcine elastin peptides stimulated the migration of fibroblasts, with the optimal response occurring at 10 -1 μg/ml, while maximal response was at 10 2 μg/ml for bonito elastin peptides. Furthermore, pretreatment of fibroblasts by lactose depressed their ability to migrate in response to all elastin peptides, suggesting the involvement of elastin receptor in cell response. These results suggest that both mammalian and piscine elastin peptides can be applied as useful biomaterials in which elasticity, antithrombotic property, and the enhancement of cell migration and proliferation are required. © 2010 European Peptide Society and John Wiley & Sons, Ltd.


Zhang W.,Fudan University | Okimura T.,Hayashikane Sangyo Co. | Xu L.,Fudan University | Zhang L.,Fudan University | And 5 more authors.
Oncotarget | Year: 2016

Our previous study demonstrated that ascophyllan, a sulfated polysaccharide purified from brown alga, has immune-activating effects. In this study, we evaluated ascophyllan as an adjuvant for its therapeutic and preventive effect on tumor in a mouse melanoma model. Ascophyllan induced migration of DCs to spleen and tumor-draining lymph node (drLN) in a mouse B16 melanoma model. Moreover, ascophyllan induced activation of dendritic cells (DCs), and promoted IFN-?- and TNF-a-producing Th1 immune responses in tumor-bearing mice. In addition, treatment with a combination of ascophyllan and ovalbumin (OVA) in the tumor-bearing mice promoted proliferation of OVA-specific CD4 and CD8 T cells and migration of those cells into the tumor, consequently inhibiting the tumor growth. Immunization with the combination of ascophyllan and OVA caused enhanced OVA-specific antibody production and memory T cell responses compared to OVA immunization alone, and almost completely prevented B16-OVA tumor growth upon subsequent tumor challenge. Finally, the combination of ascophyllan and OVA prevented B16-OVA tumor invasion and metastasis into the liver. Thus, these results demonstrate that ascophyllan can function as an adjuvant to induce DC activation, antigen specific CTL activation, Th1 immune response and antibody production, and hence may be useful as a therapeutic and preventive tumor vaccine.


Zhang W.,Fudan University | Du J.-Y.,Fudan University | Jiang Z.,Nagasaki University | Okimura T.,Hayashikane Sangyo Co. | And 3 more authors.
Marine Drugs | Year: 2014

Marine-derived sulfated polysaccharides have been shown to possess certain anti-virus, anti-tumor, anti-inflammatory and anti-coagulant activities. However, the in vivo immunomodulatory effects of marine-derived pure compounds have been less well characterized. In this study, we investigated the effect of ascophyllan, a sulfated polysaccharide purified from Ascophyllum nodosum, on the maturation of mouse dendritic cells (DCs) in vitro and in vivo. Ascophyllan induced up-regulation of co-stimulatory molecules and production of pro-inflammatory cytokines in bone marrow-derived DCs (BMDCs). Moreover, in vivo administration of ascophyllan promotes up-regulation of CD40, CD80, CD86, MHC class I and MHC class II and production of IL-6, IL-12 and TNF-α in spleen cDCs. Interestingly, ascophyllan induced a higher degree of co-stimulatory molecule up-regulation and pro-inflammatory cytokine production than fucoidan, a marine-derived polysaccharide with well-defined effect for promoting DC maturation. Ascophyllan also promoted the generation of IFN-γ-producing Th1 and Tc1 cells in the presence of DCs in an IL-12-dependent manner. Finally, myeloid differentiation primary response 88 (MyD88) signaling pathway was essential for DC maturation induced by ascophyllan. Taken together, these results demonstrate that ascophyllan induces DC maturation, and consequently enhances Th1 and Tc1 responses in vivo. This knowledge could facilitate the development of novel therapeutic strategies to combat infectious diseases and cancer. © 2014 by the authors; licensee MDPI.


Nakano K.,Nagasaki University | Kim D.,Korea Basic Science Institute | Jiang Z.,Nagasaki University | Ueno M.,Nagasaki University | And 3 more authors.
Bioscience, Biotechnology and Biochemistry | Year: 2012

Splenic natural killer (NK) cell activity against YAC-1 cells increased in mice intraperitoneally injected with ascophyllan. Ascophyllan enhanced the cytotoxicity of RAW264.7 cells toward YAC-1 cells in a concentrationdependent manner. The cytotoxicity of ascophyllanstimulated RAW264.7 cells as to YAC-1 cells was suppressed with NG-nitro-L-arginine methyl ester hydrochloride (L-NAME), an inhibitor of nitric oxide (NO) synthase, suggesting the involvement of NO in the cytotoxicity of ascophyllan-stimulated RAW264.7 cells.


Jiang Z.,Nagasaki University | Okimura T.,Hayashikane Sangyo Co. | Yokose T.,Nagasaki University | Yokose T.,11 Health | And 3 more authors.
Journal of Bioscience and Bioengineering | Year: 2010

The effects of fucose-containing sulfated polysaccharides, ascophyllan and fucoidan, isolated from the brown alga Ascophyllum nodosum, on the growth of various cell lines (MDCK, Vero, PtK1, CHO, HeLa, and XC) were investigated. In a colony formation assay, ascophyllan and fucoidan showed potent cytotoxic effects on Vero and XC cells, while other cell lines were relatively resistant to these polysaccharides. Almost no significant effects of these polysaccharides were observed in the cell lines tested using the Alamar blue cytotoxicity assay over 48 h with varying initial cell densities (2500-20,000 cells/well) in growth medium. Interestingly, a significant growth promoting effect of ascophyllan on MDCK cells was observed, whereas treatment with fucoidan showed growth suppressive effects on this cell line under the same experimental conditions. These results suggest that ascophyllan is distinguishable from fucoidan in terms of their bioactivities. This is the first report of the growth promoting effects of a sulfated fucan on a mammalian cell line under normal growth conditions. © 2010 The Society for Biotechnology, Japan.


Abu R.,Nagasaki University | Jiang Z.,Nagasaki University | Ueno M.,Nagasaki University | Okimura T.,Hayashikane Sangyo Co. | And 2 more authors.
International Journal of Biological Macromolecules | Year: 2013

Antioxidant activities of sulfated polysaccharide ascophyllan from Ascophyllum nodosum was investigated in vitro by various assays, and compared with those of fucoidan. A chemiluminescence (CL) analysis using a luminol analog, L-012, showed that ascophyllan scavenges superoxide, and the activity is greater than fucoidan. However, in the presence of 10μg/ml of ascophyllan or 10μg/ml and 100μg/ml of fucoidan, slightly enhanced CL-responses were observed. Since EDTA-treatment resulted in disappearance of the enhancement effects, it was suggested that metal ions especially iron ions in the polysaccharides might be involved in this phenomenon. In fact, metal element analysis revealed that ascophyllan and fucoidan inherently contain iron and other metal elements. EDTA-treatment resulted in significant increase in Fe2+-chelating activities of these polysaccharides. In an electron spin resonance (ESR)-spin trapping analysis in which direct UV-radiation to hydrogen peroxide was used as a source of hydroxyl radical, ascophyllan and fucoidan showed potent hydroxyl radical scavenging activity with similar extent. Reducing power of ascophyllan was stronger than that of fucoidan. Our results indicate that ascophyllan can exhibit direct and potent antioxidant activity. © 2013 Elsevier B.V.


Jiang Z.,Nagasaki University | Ueno M.,Nagasaki University | Nishiguchi T.,Nagasaki University | Abu R.,Nagasaki University | And 4 more authors.
Carbohydrate Research | Year: 2013

To investigate the role of sulfate groups on the macrophage-stimulating activities of ascophyllan, we prepared desulfated ascophyllan, and its effects on RAW264.7 cells were compared with native ascophyllan. The chemical structural analysis revealed that nearly 21% of sulfate groups of ascophyllan were removed by desulfation reaction, while no significant changes in the molecular mass and monosaccharide composition occurred after desulfation. NO- and cytokine- (TNF-α and G-CSF) inducing activities of the desulfated ascophyllan on RAW264.7 cells were significantly decreased as compared to native ascophyllan. Furthermore, the activity of desulfated ascophyllan to induce reactive oxygen species (ROS) generation from RAW264.7 cells decreased to almost negligible level. Our results suggest that the level of sulfate groups of ascophyllan is an important structural element responsible for the macrophage-stimulating activities. Probably, even the limited removal of sulfate residues sensitive to desulfation reaction may result in significant decrease in the bioactivities of ascophyllan. © 2013 Published by Elsevier Ltd. All rights reserved.


Jiang Z.,Nagasaki University | Okimura T.,Hayashikane Sangyo Co. | Yamaguchi K.,Nagasaki University | Oda T.,Nagasaki University
Nitric Oxide - Biology and Chemistry | Year: 2011

Ascophyllan isolated from the brown alga Ascophyllum nodosum is a fucose-containing sulfated polysaccharide, which has similar but distinct characteristic monosaccharide composition and entire chemical structure to fucoidan. In this study, we examined the effects of ascophyllan, fucoidan isolated from A. nodosum (A-fucoidan), and fucoidan from Sigma (S-fucoidan) as a representative fucoidan derived from other source (Fucus vesiculosus) on mouse macrophage cell line RAW264.7 cells. No significant cytotoxic effects of ascophyllan and A-fucoidan on RAW264.7 cells were observed up to 1000 μg/ml, while S-fucoidan showed cytotoxic effect in a concentration-dependent manner. Ascophyllan induced extremely higher level of nitric oxide (NO) production from RAW264.7 cells than those induced by fucoidans over the concentration range tested (0-200 μg/ml). Reverse transcription polymerase chain reaction (RT-PCR) and western blot analysis revealed that expression level of inducible NO synthase (iNOS) in ascophyllan-treated RAW264.7 cells was much higher than the levels detected in the cells treated with fucoidans. Furthermore, the activities of ascophyllan to induce the secretion of tumor necrosis factor-α (TNF-α) and granulocyte colony-stimulating factor (G-CSF) from RAW264.7 cells were also greater than those induced by fucoidans especially at lower concentration range (3.1-50 μg/ml). The activities of ascophyllan to induce NO and cytokine production in mouse peritoneal macrophages were also stronger than those of fucoidans. Electrophoretic mobility shift assay (EMSA) using infrared dye labeled nuclear factor-kappa B (NF-κB) and AP-1 consensus sequences suggested that ascophyllan can strongly activate these transcription factors. Marked increase in the nuclear translocation of p65, and the phosphorylation and degradation of IκB-α were also observed in ascophyllan-treated RAW264.7 cells. Analysis using mitogen-activated protein (MAP) kinase inhibitors and western blot analysis suggested that c-Jun N-terminal kinase (JNK) and p38 MAP kinase are mainly involved in ascophyllan-induced NO production. © 2011 Elsevier Inc. All rights reserved.

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