Chuncheon Bioindustry Foundation

Gangwon, South Korea

Chuncheon Bioindustry Foundation

Gangwon, South Korea

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Kang S.-W.,Hallym University | Choi J.-S.,Hallym University | Choi Y.-J.,Hallym University | Bae J.-Y.,Hallym University | And 7 more authors.
Journal of Nutritional Biochemistry | Year: 2010

The aberrant expression of matrix metalloproteinases (MMPs) has been implicated in matrix degradation leading to angiogenesis. This study examined the inhibitory effects of isoliquiritigenin (ISL) on phorbol myristate acetate (PMA)-induced MMP production and its tissue inhibitor of MMP (TIMP) in endothelial cells. No induction of either necrotic or apoptotic cell death was observed in response to a treatment with ISL at ≤25 μM. ISL dose-dependently suppressed PMA-induced expression and activity of MMP-2 and membrane type 1-MMP at ≥1 μM while diminishing the elevated MMP-2 transcript level. In addition, ISL inhibited PMA-triggered migration and tube formation in a dose-dependent manner. ISL further increased the TIMP production up-regulated by PMA with a biphasic effect on TIMP-2 expression. This study further attempted to investigate whether a c-Jun N-terminal kinase (JNK)- or p38 mitogen-activated protein kinase (MAPK)-responsive mechanism was responsible for the MMP production and whether ISL disturbed these signaling pathways. PMA stimulated signaling of JNK and p38 MAPK, which was dampened by ≥10 μM ISL. These results demonstrate that ISL blocked JNK- or p38 MAPK-responsive pathways leading to direct MMP activation of PMA-exposed endothelial cells. Therefore, the ISL inhibition of MMP may boost a therapeutic efficacy during angiogenesis. © 2010 Elsevier Inc. All rights reserved.

PubMed | Chuncheon Bioindustry Foundation, Gyeongbuk Institute for Marine Bioindustry, Kangwon National University and Andong National University
Type: Journal Article | Journal: Marine drugs | Year: 2016

Phlorofucofuroeckol A (PFF-A), one of the phlorotannins found in brown algae, has been reported to exert anti-cancer property. However, the molecular mechanism for the anti-cancer effect of PFF-A has not been known. Activating transcription factor 3 (ATF3) has been reported to be associated with apoptosis in colorectal cancer. The present study was performed to investigate the molecular mechanism by which PFF-A stimulates ATF3 expression and apoptosis in human colorectal cancer cells. PFF-A decreased cell viability through apoptosis of human colorectal cancer cells. PFF-A increased ATF3 expression through regulating transcriptional activity. The responsible cis-element for ATF3 transcriptional activation by PFF-A was cAMP response element binding protein (CREB), located between positions -147 and -85 of the ATF3 promoter. Inhibition of p38, c-Jun N-terminal kinases (JNK), glycogen synthase kinase (GSK) 3, and IB kinase (IKK)- blocked PFF-A-mediated ATF3 expression. ATF3 knockdown by ATF3 siRNA attenuated the cleavage of poly (ADP-ribose) polymerase (PARP) by PFF-A, while ATF3 overexpression increased PFF-A-mediated cleaved PARP. These results suggest that PFF-A may exert anti-cancer property through inducing apoptosis via the ATF3-mediated pathway in human colorectal cancer cells.

Choi J.-S.,Hallym University | Bae J.I.-Y.,Hallym University | Kim D.S.,Hallym University | Li J.,Hallym University | And 3 more authors.
Journal of Agricultural and Food Chemistry | Year: 2010

Oxidized LDL (oxLDL) has been implicated in the pathogenesis of atherosclerosis accompanying lipidladen cell appearance, inflammatory responses, and vascular dysfunction. This study examined the potentials of polyphenol quercitrin to inhibit oxLDL induction of scavenger receptor A (SR-A) and CD36 involving activation of peroxisome proliferator-activated receptor gamma (PPARγ). J774A1 murine macrophages were cultured with 10 μ/mL Cu 2+-OxLDL for various times in the presence of 1-10 μmol/L quercitrin. Cu2+-OxLDL at the given concentration facilitated macrophage proliferation and enhanced oxLDL uptake. Quercitrin dampened oxLDL uptake and lipid accumulation elevated in macrophages exposed to oxLDL. Western blot analysis revealed that 10 μg/mL oxLDL upregulated expression of SR-A and CD36, which was rapidly abolished at the transcriptional levels by 10μmol/L quercitrin within 4 h. Quercitrin diminished production of proinflammatory and proatherogenic vascular endothelial growth factor that augmented through the oxLDL binding to CD36. Similarly, quercitrin repressed expression of macrophage inflammatory protein-2 and monocyte chemoattractant protein-1 involved in monocyte trafficking and macropahage migration. In addition, quercitrin attenuated oxLDLinduced transcriptional activation of PPARy leading to CD36 induction. Furthermore, quercitrin alleviated macrophage uptake of oxLDL through interfering with PKC-PPAR signaling cascades. These results demonstrate that quercitrin blocked oxLDL uptake, cholesterol influx and lipid-laden foam cell formation through inhibiting induction of SR and VEGF linked to PKCα-PPARγ-responsive pathways. Therefore, quercitrin may be an antiatherogenic agent blocking foam cell formation pertaining to induction of SR and VEGF. © 2009 American Chemical Society.

Bae J.-Y.,Hallym University | Choi J.-S.,Hallym University | Kang S.-W.,Hallym University | Lee Y.-J.,Chuncheon Bioindustry Foundation | And 2 more authors.
Experimental Dermatology | Year: 2010

Ellagic acid, a polyphenol compound present in berries and pomegranate, has received attention as an agent that may have potential bioactivities preventing chronic diseases. This study examined photoprotective effects of ellagic acid on collagen breakdown and inflammatory responses in UV (ultraviolet)-B irradiated human skin cells and hairless mice. Ellagic acid attenuated the UV-B-induced toxicity of HaCaT keratinocytes and human dermal fibroblasts. Non-toxic ellagic acid markedly prevented collagen degradation by blocking matrix metalloproteinase production in UV-B-exposed fibroblasts. Anti-wrinkle activity of ellagic acid was further investigated in hairless mice exposed to UV-B, in which it attenuated UV-B-triggered skin wrinkle formation and epidermal thickening. Topical application of 10 μmol/l ellagic acid diminished production of pro-inflammatory cytokines IL-1β and IL-6, and blocked infiltration of inflammatory macrophages in the integuments of SKH-1 hairless mice exposed to UV-B for 8 weeks. In addition, this compound mitigated inflammatory intracellular cell adhesion molecule-1 expression in UV-B-irradiated keratinocytes and photoaged mouse epidermis. These results demonstrate that ellagic acid prevented collagen destruction and inflammatory responses caused by UV-B. Therefore, dietary and pharmacological interventions with berries rich in ellagic acid may be promising treatment strategies interrupting skin wrinkle and inflammation associated with chronic UV exposure leading to photoageing. © 2010 John Wiley & Sons A/S.

Wang Z.,Hallym University | Hwang S.H.,Hallym University | Lee S.Y.,Chuncheon Bioindustry Foundation | Lee S.Y.,Frontbio Co. | Lim S.S.,Hallym University
Nutrition Research and Practice | Year: 2016

BACKGROUND/OBJECTIVES: Jerusalem artichoke has inhibitory activity against α-glucosidase and decreases fasting serum glucose levels, which may be related to its fructan content. The biological activity of fructan can be influenced by the degree of polymerization. Thus, in this study, the inhibitory effects of original and fermented purple Jerusalem artichoke (PJA) on α-glucosidase were compared in vitro. Additionally, the anti-diabetes effect of Lactobacillus plantarum-fermented PJA (LJA) was studied in a non-insulin-dependent diabetes mellitus animal model (C57BIKsJ db/db). MATERIALS/METHODS: The water extract of PJA was fermented by L. plantarum, and two strains of Bacillus subtilis to compare their anti-α-glucosidase activities in vitro by α-glucosidase assays. The anti-diabetes effect of LJA was studied in a non-insulin-dependent diabetes mellitus animal model (C57BIKsJ db/db) for seven weeks. During the experiment, food intake, body weight, and fasting blood glucose were measured every week. At the end of the treatment period, several diabetic parameters and the intestinal α-glucosidase activity were measured. RESULTS: The LJA showed the highest α-glucosidase inhibitory activity in vitro. In the in vivo study, it resulted in a significantly lower blood glucose concentration than the control. Serum insulin and HDL cholesterol levels were significantly higher and the concentrations of triglycerides, non-esterified fatty acids, and total cholesterol were significant lower in mice treated with LJA after seven weeks. In addition, the intestinal α-glucosidase activity was partially inhibited. CONCLUSIONS: These results suggested that LJA regulates blood glucose and has potential use as a dietary supplement. © 2016 The Korean Nutrition Society and the Korean Society of Community Nutrition.

Surayot U.,Gangneung - Wonju National University | Wang J.,Northwest University, China | Seesuriyachan P.,Chiang Mai University | Kuntiya A.,Chiang Mai University | And 5 more authors.
International Journal of Biological Macromolecules | Year: 2014

Exopolysaccharides (EPS) obtained from the culture medium of Lactobacillus confusus TISTR 1498 were investigated to determine their molecular characteristics and the effect of molecular weight (Mw) on immunomodulatory activity. The EPS mainly consisted of carbohydrates (81.9±2.4%) with only one type of monosaccharide, D-glucose, which was mostly connected by α-(1→6) glycosidic linkages. The EPS itself was unable to stimulate RAW264.7 cells to produce pro-inflammatory mediator nitric oxide (NO) and cytokines. However, considerable stimulation of RAW264.7 cells was observed by the low Mw of EPSs having Mw values≤70×103g/mol. The partially hydrolyzed EPS stimulated RAW264.7 cells to induce considerable NO and various cytokine production such as TNF-α, IL-1β, IL-6 and IL-10 via up-regulation of their mRNA expression. In addition, the degradation Iκ-B and the phosphorylation of c-Jun NH2-terminal kinase (JNK) were facilitated by BW-30 and MW-40, suggesting that the partially hydrolyzed EPS stimulated RAW264.7 cells through the activation of NF-κB and JNK pathways. © 2014 Elsevier B.V.

Kang S.-W.,Hallym University | Kim M.S.,Hallym University | Kim H.-S.,Hallym University | Lee Y.-J.,Chuncheon Bioindustry Foundation | Kang Y.-H.,Hallym University
International Journal of Molecular Medicine | Year: 2012

The proliferation and migration of vascular smooth muscle cells (SMCs) play critical roles in intimal thickening and neointimal hyperplasia in early-phase atherosclerosis. This study tested whether wild grape extract (WGE) suppressed the proliferation and migration of human aortic SMCs induced by neighboring macrophages. Cellular expression of fibrogenic connective tissue growth factor (CTGF) and secretion of collagen IV and matrix metalloproteinase (MMP)-2 were determined in SMCs exposed to THP-1-differentiated macrophage-conditioned media. Proliferation was enhanced in SMCs exposed to macrophage-conditioned media collected during the early stage of differentiation, which was attenuated by treatment with ≥10 μg/ml WGE. Increased secretion of CTGF and collagen IV macrophage-conditioned media was suppressed in WGE-supplemented SMCs. TGF-β1-promoted production of CTGF and collagen IV was suppressed by blocking TGF-β receptors of R1 and R2 in SMCs. WGE repressed macrophage-conditioned media-upregulated MMP-2 secretion, indicating that WGE had an ability to encumber plaque rupture within atherosclerotic lesions. In addition, ≥1 μg/ml WGE ameliorated the migration of SMCs promoted by neighboring macrophages. These results demonstrate that WGE retarded neointimal hyperplasia and thickening within atherosclerotic plaques largely comprising of macrophages and SMCs. Therefore, WGE may be developed as an anti-proliferative and anti-migratory agent targeting SMCs in the proximity of newly differentiated and resident macrophages.

Kim D.H.,Hyundai Pharmaceutical Co. | Lee S.,Chuncheon Bioindustry Foundation | Chung Y.W.,Yonsei University | Kim B.M.,Yonsei University | And 3 more authors.
BioMed Research International | Year: 2016

Diabetes and obesity represent the major health problems and the most age-related metabolic diseases. Protein-tyrosine phosphatase 1B (PTP1B) has emerged as an important regulator of insulin signal transduction and is regarded as a pharmaceutical target for metabolic disorders. To find novel natural materials presenting therapeutic activities against diabetes and obesity, we screened various herb extracts using a chip screening allowing the determination of PTP1B inhibitory effects of the tested compounds using insulin receptor (IR) as the substrate. Cudrania tricuspidata leaves (CTe) had a strong inhibitory effect on PTP1B activity and substantially inhibited fat accumulation in 3T3-L1 cells. CTe was orally administrated to diet-induced obesity (DIO) mice once daily for 3 weeks after which changes in glucose, insulin metabolism, and fat accumulation were examined. Hepatic enzyme markers (aspartate aminotransferase, AST, and alanine aminotransferase, ALT) and total fat mass and triglyceride levels decreased in CTe-treated mice, whereas body weight and total cholesterol concentration slightly decreased. CTe increased the phosphorylation of IRS-1 and Akt in liver tissue. Furthermore, CTe treatment significantly lowered blood glucose levels and improved insulin secretion in DIO mice. Our results strongly suggest that CTe may represent a promising therapeutic substance against diabetes and obesity. Copyright © 2016 Dae Hoon Kim et al.

Seo Y.C.,Kangwon National University | Song C.H.,Kangwon National University | Lim H.W.,Chuncheon Bioindustry Foundation | Lee H.Y.,Seowon University
Biotechnology Progress | Year: 2013

This study investigated the effects of ultrasonication extraction (UE) on the immunomodulatory activity of low-quality ginseng. The results indicate that the optimal conditions for extracting low-quality ginseng are ultrasonication at 60 kHz and 85°C for 60 min. The extraction yield from the UE was 20% higher than that of the water extraction (WE) at 100°C. The low quality ginseng obtained from the UE exhibited relatively low cytotoxicity toward normal human cells, with an observed toxicity of 15-18% at a concentration of 1.0 mg/mL. The ginseng product obtained following UE induced human B and T cells growth and resulted in concentrations of up to 9.33 × 104 cells/mL and 15.33 × 104 cells/mL, respectively. The ginseng extract also increased the secretion of interleukin-6 and tumor necrosis factor-α from these cells by up to 35%, and natural killer/cell growth was also improved by up to 30%. The UE effectively released 2- to 3-fold higher levels of ginsenosides than the WE. Specifically, the obtained levels of Rb1, Re, and Rg1, which are likely immunomodulatory factors, were approximately three times higher after ultrasonication than after WE. These results were further supported by the finding that UE product-treated macrophages produced higher levels of nitric oxide (21 μM) than macrophages treated with the WE product or with standard ginsenosides. These results demonstrate that this optimized ultrasonication process effectively destroyed the more rigid cell walls of low-quality ginseng and released high levels of ginsenosides. This work is the first to correlate extraction parameters with both extraction yields and biological activity. The use of low-quality ginseng can thus be expanded by utilizing a low-temperature ultrasonic extraction process. © 2012 American Institute of Chemical Engineers (AIChE).

Cao R.-A.,Heilongjiang Bayi Agricultural University | Cao R.-A.,Gangneung - Wonju National University | Lee Y.,Chuncheon Bioindustry Foundation | You S.,Gangneung - Wonju National University
International Journal of Biological Macromolecules | Year: 2014

Water-soluble sulfated fucans isolated from Ecklonia cava were fractionated using an anion-exchange chromatography to investigate their molecular characteristics and immunomodulating activities. The crude fucoidan extract and purified fractions (EF1, EF2, and EF3) consisted mostly of different ratios of neutral sugars, proteins, sulfates, uronic acids, and their monosaccharide compositions were also significantly different. The backbone of the most immunoenhancing fraction, EF2, was mainly linked by (1→3)-linked fucopyranosyl and (1→4)-linked mannopyranosyl residues with sulfates at C-4 of fucopyranosyl units. The molecular weights of the crude fucoidan extract and purified fractions ranged from 8.3×103 to 442.6×103g/mol. The crude extract, EF1 and EF2 stimulated RAW264.7 cells to produce considerable amounts of nitric oxide and cytokines. The treatment of cells with the sulfated fucans induced the degradation of Iκ-B and the phosphorylation of MAPK in RAW264.7 cells, implying that they might stimulate RAW264.7 cells through the activation of NF-κB and MAPK pathways. © 2014 Elsevier B.V.

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