• Biomolecules & Therapeutics
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• v.17 no.3
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• pp.325-331
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• 2009

The object of this study was to evaluate the single oral dose toxicity of Low Molecular Weight Fucoidan (LMF) in male and female rats. LMF was administered to female and male SD rats as an oral dose of 2,000, 1,000 and 500 mg/kg (body wt.). Animals were monitored for the mortality and changes in body weight, clinical signs and gross observation organ weight and histopathology of 14 principle organs were examined upon necropsy. As the results, no LMF treatment related mortalities, clinical signs, changes on the body and organ weights, gross and histopathological observations against 14 principle organs were detected up to 2,000 mg/kg in both female and male rats except for some sporadic findings not LMF treatment related toxicological signs. Therefore, $LD_{50}$ (50% lethal dose) and approximate LD of LMF after single oral treatment in female and male rats were considered over 2,000 mg/kg - the limited dosages recommended by KFDA Guidelines [2005-60, 2005], respectively.

• Korean Journal of Food Science and Technology
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• v.40 no.5
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• pp.545-550
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• 2008

The anticancer and immunomodulatory activities of low molecular weight (Mw 11 kDa) fucoidan isolated from Hizikia fusiforme (H. fusiforme) via the ultrasonification extraction process were assessed in this study. Low molecular weight fucoidan improved the growth of human B and T cells, up to approximately 40% as compared to the controls (untreated) and 30% for commercially available fucoidan (Mw 150 kDa). IL-6 and TNF-$\alpha$ were secreted from human B cells at levels of $7.8\times10^{-4}$ pg/mL and $7.2\times10^{-4}$ pg/mL, respectively, and these levels were higher than the levels measured in the controls and with other high molecular weight fucoidan. It was also determined that the cytokine from human B and T cells cultivated with added fucoidan enhanced the growth of human NK cells. The fucoidan isolated from H. fusiforme showed low cytotoxicity, approximately 19%, after the addition of 1.0 mg/mL, the highest tested concentration. The growth of human lung cancer cells (A549) and human breast cancer cells (MCF-7) were inhibited by 69.8% and 83.3%, respectively. These results demonstrated that the low molecular weight fucoidan isolated from H. fusiforme has potential as a new functional food component that evidences immunomodulatory activities and anticancer activity. One of the primary positive features of this fucoidan is that low molecular weight polysaccharides can be readily handled during processing.

• Toxicological Research
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• v.24 no.1
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• pp.79-86
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• 2008

This study was conducted to obtain information of the oral dose toxicity of low molecular fucoidan (LMF) in male and female mice. In order to calculate 50% lethal dose ($LD_{50}$) and approximate lethal dose (LD), test material was once orally administered to male and female ICR mice at dose levels of 2000, 1000, 500, 250, 125 and 0 (vehicle control) mg/kg (body wt.). The mortality and the changes on body weight, clinical signs, gross observation and organ weight and histopathology of principle organs were monitored 14 days after LMF treatment. We could not find any mortalities, clinical signs, body weight changes and gross findings. In addition, significant changes in the organ weight and histopathology of principal organs were not observed except for some sporadic findings. The results obtained in this study suggest that LMF may not be toxic in mice and may be therefore safe for clinical use. The $LD_{50}$ and approximate LD in mice after single oral dose of LMF were considered over 2000 mg/kg in both female and male mice.

• Korean Chemical Engineering Research
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• v.46 no.5
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• pp.886-891
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• 2008

Contact glow discharge electrolysis(CGDE) is an unconventional electrolysis where plasma is sustained by D.C. glow discharge between an electrode and the surface of electrolyte surrounding it at high voltage. In this study, the behavior of CGDE in NaCl solution and the depolymerization of fucoidan by CGDE were investigated. After onset of CGDE, increase of voltage enhanced Glow discharge which resulted in low current density and low temperature in NaCl electrolyte. From the variation of molecular weight of fucoidan with the reaction time, it was demonstrated that the degradation of fucoidan followed a first-order rate law. Molecular weight of fucoidan treated with CGDE was about 40 times lower compared to initial fucoidan without content decrease of sulfate and fucos.

• Biomolecules & Therapeutics
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• v.18 no.1
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• pp.111-121
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• 2010

In order to investigate the preliminary repeat oral dose toxicity and to determine the highest dosage for further 4-week repeated dose toxicity test, Low Molecular Weight Fucoidan (LMF) has been showed various pharmacological effects, was orally administered to female and male rats, once a day for 14 days at dose levels of 2,000, 1,000, 500 and 0 (vehicle control) mg/kg (body weights) in a volume of 10 ml/kg. The mortality and changes on the body weights, clinical signs, hematology, serum biochemistry and gross observations were monitored with organ weight and histopathology of principle organs. As the results of 14-day repeated oral treatment of LMF, no LMF treatment related mortalities were detected up to 2,000 mg/kg in both male and female rats, respectively. In addition, no noticeable changes on the body weight and clinical signs were detected except for significant decreases on the body weights and gains restricted to male 2,000 mg/kg treated groups as compared with male vehicle control. No meaningful changes on the organ weights, hematological, serum biochemistrical, gross and histopathological findings were observed. Therefore the highest dosage in the 4-week repeated dose toxicity test is suggested as 2,000 mg/kg in both female and male rats, respectively.

• Korean Journal of Agricultural Science
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• v.36 no.1
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• pp.41-50
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• 2009

Fucoidan is a uniquely-structured sulfated fucose-rich polysaccharide derived from brown algae. Recently, the abalone glycosidase-digested fucoidan extract (fucoidan extract) derived from seaweed Cladosiphon novae-caledoniae Kylin (Mozuku) draws much attention because of its clinical anti-cancer effect in Japan. Here, we report the cancer cells-specific apoptosis inducing effects of the fucoidan extract. The fucoidan extract suppressed the growth of various anchorage-dependent and -independent cancer cells. The fucoidan extract contained low molecular weight components, which induced apoptosis of human leukemic HL 60 cells but not of human lymphocytes. It was shown that the fucoidan extract lead caspase 3/7 activation and loss of mitochondrial membrane potential in HL 60 cells. Another function of the fucoidan extract was also observed. It has been known that sugar chain expression on the surface of cancer cell membrane changes dependent on their malignancy. The analysis on sugar chain expression profiling using FITC-labeled lectins revealed that the expression of concanavalin A (Con A) binding sugar chain was enhanced by the treatment of human lung adenocarcinoma A549, human uterine carcinoma HeLa and human fibrosarcoma HT1080 cells with the fucoidan extract. Con A-induced apoptosis of cancer cells was stimulated in a dose-and time-dependent manner by the treatment with the fucoidan extract but not of human normal fibroblast TIG-1 cells.

• Journal of Microbiology and Biotechnology
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• v.32 no.8
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• pp.1017-1025
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• 2022

Bone homeostasis is regulated by constant remodeling through osteogenesis by osteoblasts and osteolysis by osteoclasts and osteoporosis can be provoked when this balance is broken. Present pharmaceutical treatments for osteoporosis have harmful side effects and thus, our goal was to develop therapeutics from intrisincally safe natural products. Fucoidan is a polysaccharide extracted from many species of brown seaweed, with valuable pharmaceutical activities. To intensify the effect of fucoidan on bone homeostasis, we hydrolyzed fucoidan using AMG, Pectinex and Viscozyme. Of these, fucoidan biotransformed by Pectinex (Fu/Pec) powerfully inhibited the induction of tartrate-resistant acid phosphatase (TRAP) activity in osteoclasts differentiated from bone marrow macrophages (BMMs) by the receptor for activation of nuclear factor-κB ligand (RANKL). To investigate potential of lower molecular weight fucoidan it was separated into >300 kDa, 50-300 kDa, and <50 kDa Fu/Pec fractions by ultrafiltration system. The effects of these fractions on TRAP and alkaline phosphatase (ALP) activities were then examined in differentiated osteoclasts and MC3T3-E1 osteoblasts, respectively. Interestingly, 50-300 kDa Fu/Pec suppressed RANKL-induced osteoclasts differentiation from BMMs but did not synergistically enhance osteoblasts differentiation induced by osteogenic agents. In addition, this fraction inhibited the expressions of NFATc1, TRAP, OSCAR, and RANK, which are all key transcriptional factors involved in osteoclast differentiation, and those of Src, c-Fos and Mitf, as determined by RT-PCR. In conclusion, enzymatically low-molecularized 50-300 kDa Fu/Pec suppressed TRAP by downregulating RANKL-related signaling, contributing to the inhibition of osteoclasts differentiation, and represented a potential means of inducing bone remodeling in the background of osteoporosis.

• Korean Chemical Engineering Research
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• v.50 no.2
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• pp.238-243
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• 2012

Laminaria roots have not been practically used in Korea. In this study, the extraction process of carbohydrates and minerals from Laminaria roots was investigated and the properties of extracted components were measured. Hydrochloric acid generally used in carbohydrate extraction from seaweeds in order to obtain high extraction yield. But in this work, to utilize extracted components as a functional food material, organic acids such as citric acid were used. Organic acid as extraction solvent has low extraction yield compared to strong acids. Therefore optimum condition for maximum yield was investigated in carbohydrate extraction from Laminaria roots using organic acid. We measured the extraction yields of carbohydrate with variation of extraction temperature, extraction time, concentration of organic acid and particle size of samples. The extraction yield increased as the particle size decreased and temperature became high. The extraction yield was 19.0 wt% after 4.0 hours extraction with 0.2 wt% citric acid at $100^{\circ}C$. Potassium concentration was high compared other minerals in extraction solution, that is, the ratio of K/Na was about 3.0. Fucoidan from Laminaria roots had same carbohydrate composition and lower molecular weight compared that of Undaria pinnatifida.

• Korean Journal of Food Science and Technology
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• v.40 no.5
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• pp.522-527
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• 2008

Low molecular peptides were isolated from Asterias amurensis via SDS-PAGE. The peptides were separated via consecutive gel filtration as five fractions (F1-F5) according to molecular weights, based on the results of MALDI-TOF MS analysis. The molecular weight of the most active peptide was estimated as 15,000 daltons. The peptide showed cytotoxicity on normal human fibroblast cells at levels as low as 20% when 1.0 mg/mL of the samples was added. The peptide also exhibited higher levels of nitric oxide production from macrophages than the lipopolysaccaharides. It was determined that prostaglendin $E_2$ production was significantly inhibited, up to 127.8% as compared to the control. The low molecular peptide inhibited hyaluronidase activity as 535.7 ${\mu}g/mL$ of $IC_{50}$. It can be concluded that the relatively low molecular weight peptide, fucoidan, from A. amurensis has excellent cosmetic and immunomodulatory activities, which can be considered as a possible resource of new cosmetic agents for skin immunomodulation.