• BMB Reports
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• v.47 no.11
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• pp.649-654
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• 2014

Neutrophils play an important role in the initiation of innate immunity against infection and injury. Although many different types of G-protein coupled receptors are functionally expressed in neutrophils, no reports have demonstrated functional expression of umami taste receptor in these cells. We observed that mouse neutrophils express the umami taste receptor T1R1/T1R3 through RNA sequencing and quantitative RT-PCR analysis. Stimulation of mouse neutrophils with L-alanine or L-serine, which are ligands for the umami taste receptor, elicited not only ERK or p38 MAPK phosphorylation but also chemotactic migration. Moreover, addition of L-alanine or L-serine markedly reduced the production of several cytokines including $TNF-{\alpha}$ induced by lipopoly-saccharide (LPS) through inhibition of $NF-{\kappa}B$ activity or STAT3 phosphorylation in neutrophils. Our findings demonstrate that neutrophils express the umami taste receptor, through which tastants stimulate neutrophils, resulting in chemotactic migration, and attenuation of LPS-induced inflammatory response.

• Archives of Pharmacal Research
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• v.29 no.12
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• pp.1158-1163
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• 2006

More than 95% of lead, a environmental heavy metal, entering into blood accumulates in erythrocytes suggesting erythrocytes as an important target of lead toxicity. Recent studies reported that erythrocytes could contribute to blood coagulation via phosphatidylserine (PS) exposure in erythrocytes. However, in vivo effects of chronic lead exposure especially by drink-ing water on procoagulant activity of erythrocytes have not been studied yet. In the present study, we investigated the effects of chronic exposure of lead by drinking water on erythrocytes in rats. Groups of 40 male rats were provided with drinking water containing various concentrations of lead for 4 weeks and complete blood cell count, procoagulant activities of erythrocytes and platelets were evaluated with basic inspections on body weight and food/water consumption. The administration of lead containing drinking water increased the blood lead level (BLL) in a dose-dependent manner up to $22.39{\pm}2.26\;{\mu}g/dL$. Water consumption was significantly decreased while food consumption or body weight gain was not affected. In contrast to the previous findings with acute lead exposure, chronic lead exposure failed to increase PS exposure in erythrocytes with statistical significance although some trends of enhancement were observed. It implies that a certain adaptation might have happened in body during repeated exposure to lead, resulting in attenuation of PS exposure. With this study, we believe that a valuable information was provided for the study on the toxicological significance and the risk assessment of lead contaminated drinking water.

• Journal of Oriental Neuropsychiatry
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• v.20 no.1
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• pp.235-247
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• 2009

Objectives : Ginseng Radix Rubra water extract(RGE) has been used in vivo test for its beneficial effects on neuronal survival and neuroprotective functions, particularly in connection with APP-related dementias and Alzheimer's disease (AD). APP derived from proteolytic processing of the ${\beta}$-amyloid precursor protein (APP), including the amyloid-${\beta}$ peptide (A${\beta}$), plays a critical role in the pathogenesis of Alzheimer's dementia. Methods : We determined that RGE inhibits formation of APP, which are the behavior, and possibly causative, feature of AD. Results and Conclusions : In the cells, RGE significantly activated antiapoptosis and decreased the activity of APP-grim, a key enzyme in the apoptosis cell-signaling cascade. These results suggest that neuronal damage in AD might be due to two factors: a direct APP toxicity and multiple cellular and molecular neuroprotective mechanisms, including attenuation of apoptosis and direct inhibition of APP, underlie the neuroprotective effects of RGE.

• Nutritional Sciences
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• v.7 no.4
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• pp.214-217
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• 2004

Dietary intervention and simvastatin is beneficial in the prevention cardiovascular diseases by lowering plasma lipid levels. Endothelial dysfunction is associated with coronary artery disease and its risk factors and is reversed by dietary intervention. It has been suggested that hyperlipidemia contributes to the development of atherosclerosis by increasing inducible nitric oxide synthase (iNOS) expression via intimal thickening. Statins treatment has been found to decrease iNOS expression and atherogenensis in animal models. We hypothesized that dietary intervention and simvastatin therapy could decrease plasma nitric oxide in hypercholesterolemic patients, which would suggest the opportunity for modulation of iNOS expression through the use of statins in a clinical situation. We measured the plasma levels of nitrite and nitrate (NOx) in 19 hyperlipidemia patients. The subjects were under dietary intervention following simvastatin therapy for 12 weeks. As a result, the plasma level of NOx, stable metabolites of nitric oxide (NO), saw a two-fold elevation in hyperlipidemic patients as compared to normal levels. Although 12 weeks of dietary intervention did not lower NOx levels, subsequent 12-week simvastatin (10 mg/day) treatment, along with dietary intervention, lowered NOx levels significantly. This NOx reduction, induced by simvastatin therapy, positively correlated with lowered coronary risk factors (r=0.40, p=0.02). It indicated that simvastatin therapy decreases plasma NOx levels by, perhaps, decreasing iNOS expression or activity leading to the attenuation of the development of neointima.

• Nutrition Research and Practice
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• v.8 no.4
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• pp.398-403
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• 2014

BACKGROUND/OBJECTIVES: Ultraviolet B (UVB) irradiation on skin can induce production of reactive oxygen species (ROS), which cause expression of matrix metalloproteinases (MMPs) and collagen degradation. Thus, chronic exposure of skin to UVB irradiation leads to histological changes consistent with aging, such as wrinkling, abnormal pigmentation, and loss of elasticity. We investigated the protective effect of the standardized green tea seed extract (GSE) on UVB-induced skin photoaging in hairless mice. MATERIALS/METHODS: Skin photoaging was induced by UVB irradiation on the back of Skh-1 hairless mice three times per week and UVB irradiation was performed for 10 weeks. Mice were divided into six groups; normal control, UVB irradiated control group, positive control (UVB + dietary supplement of vitamin C 100 mg/kg), GSE 10 mg/kg (UVB + dietary supplement of GSE 10 mg/kg), GSE 100 mg/kg (UVB + dietary supplement of GSE 100 mg/kg), and GSE 200 mg/kg (UVB + dietary supplement of GSE 200 mg/kg). RESULTS: The dietary supplement GSE attenuated UVB irradiation-induced wrinkle formation and the decrease in density of dermal collagen fiber. In addition, results of the antioxidant analysis showed that GSE induced a significant increase in antioxidant enzyme activity compared with the UVB irradiation control group. Dietary supplementation with GSE 200 mg/kg resulted in a significant decrease in expression of MMP-1, MMP-3, and MMP-9 and an increase in expression of TIMP and type-1 collagen. CONCLUSIONS: Findings of this study suggest that dietary supplement GSE could be useful in attenuation of UVB irradiation-induced skin photoaging and wrinkle formation due to regulation of antioxidant defense systems and MMPs expression.

• Journal of the Korean Society of Food Science and Nutrition
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• v.37 no.11
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• pp.1389-1394
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• 2008

This study was carried out to investigate antioxidative and hepatoprotective effects of Acer tegmentosum M. (ATM) extracts. Content of total polyphenol of EtOAc fraction was the highest amount among fractions. Electron donating abilities of all fractions were increased as concentrations of each fraction were increased. ATM BuOH fraction showed the highest SOD like activity at low concentration (<$250\;{\mu}g/mL$). To investigate the protective effect of ATM on hepatotoxicity, ATM BuOH fraction was administered to mice for 7 consecutive days, and then lipopolysaccharide (LPS) was injected at a dosage of 1 mg/kg. The LPS led to increase of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and blood urea nitrogen (BUN). However, pretreatment with BuOH fraction prior to LPS injection significantly decreased plasma hepatospecific enzyme levels. Histological findings demonstrated that pretreatment with BuOH fraction resulted in an attenuation of LPS induced liver damages.

• The Korea Journal of Herbology
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• v.23 no.4
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• pp.121-134
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• 2008

Objectives: Melia toosendan(MT) has been used as a traditional Korean herbal medicine, and today it is used as a medication for colic, side aches, heartache and other disorders of liver. The aim of this study was to determine whether fractionated extracts of MT inhibit free radical generation such as DPPH radical, superoxide radical and nitric oxide, production of nitrite, an index of NO, PGE2, iNOS, COX-2 and proinflammatory cytokines in lipopolysaccharide(LPS)-treated RAW 264.7 macrophages. Methods: MT extract prepared with methanol, and then fractionated with hexane, dichloromethane, ethylacetate, n-butanol and water. Inhibitory effect of MT onto free radical generation was determined by measuring DPPH, superoxide anions and nitric oxide scavenging activities in vitro. Cytotoxic activity of extracts on RAW 264.7 cells was measured using 5-(3-caroboxymeth-oxyphenyl)-2H-tetra-zolium inner salt(MTS) assay. Intracelluar oxidation was analysed by DCF-DA assay. The nitric oxide(NO) production was measured by Griess reagent system. The levels of iNOS and COX-2 expression were confirmed by western blot. And pro inflammatory cytokines were measured by ELISA kit. Results: Our results indicated that fractionated extracts, especially dichloromethane and ethyl acetate extracts, significantly inhibited free radical generation, the LPS-induced $H_2O_2$, NO, $PGE_2$ production and iNOS, COX-2 expression accompanied by an attenuation of TNF-${\alpha}$, IL-1${\beta}$ and IL-6 formation in macrophages. Conclusions: These results indicate that dichloromethane and ethyl acetate extracts of MT have potential as an agent of chronic inflammatory diseases.

• The Journal of Internal Korean Medicine
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• v.36 no.2
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• pp.105-121
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• 2015

Objectives: This study investigated the effects of Gagam-daewhang mangcho-tang (GDM) and its components on cerulein-induced acute pancreatitis (AP) in mice Methods: The AP mouse model was induced by intra-peritoneal injection of cerulein (50 μg/kg) at hourly intervals for 6 times. The experimental drug was administrated intraperitoneally 1 hour prior to the first injection of cerulein. Mice were sacrificed at 6 hours after the last injection of cerulein. Blood samples were taken to determine serum amylase level. The pancreas and lungs were rapidly removed for histochemical examination and myeloperoxidase (MPO) assays. Results: Administration of modified GDM significantly reduced the ratio of pancreas/body weight, level of serum amylase, neutrophil infiltration, and histological damage of the pancreas and lung. In a test of the components of GDM, the Salvia miltiorrhiza (SM) group showed a significant suppression of the severity of AP. In an experiment testing the concentration of SM, the 150 mg/kg SM group showed significant attenuation of the severity of AP. Conclusions: Modified GDM and a SM water extract could attenuate AP and AP-associated lung injury via suppression of digestive enzyme secretion and MPO activity.

• Korean Journal of Pharmacognosy
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• v.47 no.3
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• pp.280-286
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• 2016

Helianthus tuberosus Linne (Compositae) has been widely used as a folk remedy to treat various ailments including fever, bleeding, fracture and contusion. This study was designed to elucidate the lifespan extending activities MeOH extract of the tubers of Helianthus tuberosus Linne (MHT) using Caenorhabditis elegans (C. elegans) model system. In the current study, we found that the lifespan of worms was significantly extended by MHT supplement, dose-dependently. MHT also provided robust protection against various stress environments such as osmotic, thermal and oxidative condition. In addition, elevated antioxidant enzyme activities by MHT resulted in attenuation of intracellular reactive oxygen spices (ROS) levels, suggesting antioxidant capacity of MHT might be associated with longevity properties. Herein, we showed that altered food intake and growth of worms were also involved in the MHT activity. Furthermore, MHT increased body movement in aged worms, indicating possible role for MHT in healthspan.

• Fisheries and Aquatic Sciences
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• v.16 no.3
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• pp.149-158
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• 2013

We demonstrate enhanced growth, innate immunity and protection against hydrogen peroxide ($H_2O_2$)-induced protein oxidation and cellular DNA damage in olive flounder Paralichthys olivaceus fed a chitosan-coated moist pallet (MP) diet. A chitosan-based biopolymer coated MP as the experimental diet and a non-coated MP (control) was fed to olive flounder fish. Growth, including the average weight gain (g/fish), weight gain (%) and feed intake (g) of the fish group fed a chitosan-coated MP diet increased significantly. The survival rate was reported as 100% throughout the experimental period. Immunological parameters indicated higher mucus lysozyme activity and significantly higher fish skin mucus total protein content was observed in fish fed the chitosan-coated MP diet compared to the control. A blood plasma analysis revealed attenuation of cellular DNA and protein oxidative damage caused by $H_2O_2$-induced oxidative stress in the fish fed the chitosan-coated MP diet compared to the control group. Moreover, blood serum biochemical analysis revealed health-promoting effects, including significantly higher hemoglobin and total cholesterol levels in the fish fed the chitosan-coated MP diet compared to the control group. In conclusion, growth, innate immunity and protection against oxidative stresses were improved by feeding of the chitosan-coated MP diet to olive flounder reared in aquaculture.