• 한국식품영양과학회지
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• 제44권10호
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• pp.1450-1457
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• 2015

톳은 여러 생리활성이 알려져 있는 해조류로 본 연구에서는 톳의 활용 가능성을 확장시키기 위하여 유산균의 종류를 달리하여 발효한 톳을 시료로 하고 추출물 단계에서 항염증 효과를 비교하였다. 유산균인 Weissella sp. SH-1과 Lactobacillus casei를 접종하여 발효시킨 톳 추출물은 무접종군에 비하여 높은 NO 억제 활성을 나타내었으며, 유산균간의 비교에서는 Weissella sp. SH-1 접종군보다 L. casei 접종군에서 NO 생성 억제 효과가 높게 나타났다. 중요 염증 유발인자인 iNOS, COX-2 및 IL-6의 발현을 비교한 결과 Weissella sp. SH-1 접종군에 의한 iNOS 억제능이 높았으며 COX-2, IL-6 발현은 L. casei 접종군에 의해 효과적으로 억제되었다. 유산균에 의한 염증 유발인자 억제능에 대한 MAPK 신호 전달 경로를 알아본 결과 ERK, p38, JNK의 인산화에 의해 항염증 활성이 나타나는 것을 알 수 있었다. 이상의 결과로부터 유산균 Weissella sp. SH-1과 L. casei를 이용한 발효는 염증 억제에 효과가 있는 유효성분의 추출을 증진시킬 수 있음을 간접적으로 확인할 수 있었다. 향후 본 연구 결과를 바탕으로 유산균 Weissella sp. SH-1과 L. casei를 이용한 발효방법을 활용하여 기능성 식품소재 및 제품 개발에 응용이 가능할 것으로 기대된다.

• Journal of Microbiology and Biotechnology
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• 제22권4호
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• pp.494-500
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• 2012

Silk fibroin (SF) peptide has been traditionally used as a treatment for flatulence, spasms, and phlegm. In this study, we examined whether SF peptide enhanced the anti-inflammatory effect of PEP-1-FK506 binding protein (PEP-1-FK506BP) through comparing the anti-inflammatory activities of SF peptide and/or PEP-1-FK506BP. In the presence or absence of SF peptide, transduction levels of PEP-1-FK506BP into HaCaT cells and mice skin and anti-inflammatory activities of PEP-1-FK506BP were identified by Western blot and histological analyses. SF peptide alone effectively reduced both mice ear edema and the elevated levels of cyclooxygenase-2, interleukin-6 and $-1{\beta}$, and tumor necrosis factor-${\alpha}$, showing similar anti-inflammatory effect to that of PEP-1-FK506BP. Furthermore, co-treatment with SF peptide and PEP-1-FK506BP exhibited more enhanced anti-inflammatory effects than the samples treated with SF peptides or PEP-1-FK506BP alone, suggesting the possibility that SF peptide and PEP-1-FK506BP might interact with each other. Moreover, the transduction data demonstrated that SF peptide did not affect the transduction of PEP-1-FK506BP into HaCaT cells and mice skin, indicating that the improvement of anti-inflammatory effect of PEP-1-FK506BP was not caused by enhanced transduction of PEP-1-FK506BP. Thus, these results suggest the possibility that co-treatment with SF peptide and PEP-1-FK506BP may be exploited as a useful therapy for various inflammation-related diseases.

• 대한한방내과학회지
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• 제25권4호
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• pp.260-273
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• 2004

Backgrounds : In recent years, asthma has become recognized as a chronic inflammatory disease associated pathologically with airway epithelial inflammation and airway remodeling. Objectives : To evaluate the different effects of Hirudo depending upon pharmaceutical manufactures on the expression and the activities of IL-6 and GM-CSF in airway epithelial cells, samples of Hirudo(水蛭), Hirudo toasted with Talcum(水蛭滑石炒) and Hirudo toasted with Ephedrae Herba(水蛭麻黃炒) were tested. Methods : After inducing enhanced messenger RNA(mRNA) expression and secretion of each cytokine by tumor necrosis factor-alpha(10 ng/ml) treatment, cultured human bronchial epithelial cell line BEAS-2B was added to each sample$(l,\;10,\;100\;&\;1000\;{\mu}g/ml)$. Subsequently, DNA activities were analyzed. Specifically mRNA expression and culture supernatants(protein levels) of IL-6 and GM-CSF from BEAS-2B cells, were analyzed using luciferase reporter gene assay, reverse transcription-polymerase chain reaction(RT-PCR) analysis and enzyme-linked immunosorbent assay. Results : Hirudo toasted with Ephedrae Herba(水蛭麻黃炒) and Hirudo(水蛭) inhibited IL-6 activities in BEAS-2B cells remarkably, and inhibited mRNA expression levels and protein levels in supernatant of IL-6 and GM-CSF at various concentrations, significantly(p<0.05). However, Hirudo toasted with Talcum(水蛭滑石炒) had no effect on mRNA expression levels and showed a slight inhibitory effect on GM-CSF protein levels in supernatant of culture medium. Conclusions : These results strongly suggest that Hirudo toasted with Ephedrae Herba(水蛭麻黃炒) and Hirudo(水蛭) would be serve as effective medicaments in the treatment of airway inflammation and remodeling of asthmatic patients.

• Toxicological Research
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• 제33권3호
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• pp.239-253
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• 2017

Neodymium is a future-oriented material due to its unique properties, and its use is increasing in various industrial fields worldwide. However, the toxicity caused by repeated exposure to this metal has not been studied in detail thus far. The present study was carried out to investigate the potential inhalation toxicity of nano-sized neodymium oxide ($Nd_2O_3$) following a 28-day repeated inhalation exposure in male Sprague-Dawley rats. Male rats were exposed to nano-sized $Nd_2O_3-containing$ aerosols via a nose-only inhalation system at doses of $0mg/m^3$, $0.5mg/m^3$, $2.5mg/m^3$, and $10mg/m^3$ for 6 hr/day, 5 days/week over a 28-day period, followed by a 28-day recovery period. During the experimental period, clinical signs, body weight, hematologic parameters, serum biochemical parameters, necropsy findings, organ weight, and histopathological findings were examined; neodymium distribution in the major organs and blood, bronchoalveolar lavage fluid (BALF), and oxidative stress in lung tissues were analyzed. Most of the neodymium was found to be deposited in lung tissues, showing a dose-dependent relationship. Infiltration of inflammatory cells and pulmonary alveolar proteinosis (PAP) were the main observations of lung histopathology. Infiltration of inflammatory cells was observed in the $2.5mg/m^3$ and higher dose treatment groups. PAP was observed in all treatment groups accompanied by an increase in lung weight, but was observed to a lesser extent in the $0.5mg/m^3$ treatment group. In BALF analysis, total cell counts, including macrophages and neutrophils, lactate dehydrogenase, albumin, interleukin-6, and tumor necrosis factor-alpha, increased significantly in all treatment groups. After a 4-week recovery period, these changes were generally reversed in the $0.5mg/m^3$ group, but were exacerbated in the $10mg/m^3$ group. The lowest-observed-adverse-effect concentration of nano-sized $Nd_2O_3$ was determined to be $0.5mg/m^3$, and the target organ was determined to be the lung, under the present experimental conditions in male rats.

• Biomolecules & Therapeutics
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• 제26권2호
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• pp.146-156
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• 2018

Spermidine is a naturally occurring polyamine compound that has recently emerged with anti-aging properties and suppresses inflammation and oxidation. However, its mechanisms of action on anti-inflammatory and antioxidant effects have not been fully elucidated. In this study, the potential of spermidine for reducing pro-inflammatory and oxidative effects in lipopolysaccharide (LPS)-stimulated macrophages and zebrafish was explored. Our data indicate that spermidine significantly inhibited the production of pro-inflammatory mediators such as nitric oxide (NO) and prostaglandin $E_2$ ($PGE_2$), and cytokines including tumor necrosis $factor-{\alpha}$ and $interleukin-1{\beta}$ in RAW 264.7 macrophages without any significant cytotoxicity. The protective effects of spermidine accompanied by a marked suppression in their regulatory gene expression at the transcription levels. Spermidine also attenuated the nuclear translocation of $NF-{\kappa}B$ p65 subunit and reduced LPS-induced intracellular accumulation of reactive oxygen species (ROS) in RAW 264.7 macrophages. Moreover, spermidine prevented the LPS-induced NO production and ROS accumulation in zebrafish larvae and was found to be associated with a diminished recruitment of neutrophils and macrophages. Although more work is needed to fully understand the critical role of spermidine on the inhibition of inflammation-associated migration of immune cells, our findings clearly demonstrate that spermidine may be a potential therapeutic intervention for the treatment of inflammatory and oxidative disorders.

• Journal of Ginseng Research
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• 제40권3호
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• pp.203-210
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• 2016

Background: Korean Red Ginseng (KRG) is a well-known natural product with anticarcinogenic and antioxidant effects. We evaluated the antifatigue effect of KRG in patients with nonalcoholic fatty liver disease (NAFLD). Methods: Eighty patients with NAFLD were prospectively randomized to receive 3 wk of KRG or placebo in addition to counseling on healthy eating and regular exercise. Liver function test, proinflammatory cytokines, adiponectin, antioxidant activity, and fatigue score were measured and compared according to the body mass index between the KRG and placebo groups. Results: The liver function tests were significantly improved after 3 wk of treatment in both groups. The mean levels (at baseline and after treatment) of tumor necrosis factor-${\alpha}$ were $108.0pg/mL{\pm}54.8pg/mL$ and $92.7pg/mL{\pm}39.0pg/mL$ (p = 0.018) in the KRG group and $123.1pg/mL{\pm}42.1pg/mL$ and $127.5pg/mL{\pm}62.2pg/mL$ (p = 0.694) in the placebo group, respectively. There was a significant difference in change of adiponectin levels between the KRG ($7,751.2pg/mL{\pm}3,108.1pg/mL$ and $8,197.3pg/mL{\pm}2,714.5pg/mL$) and placebo groups ($7,711.6pg/mL{\pm}3,041.3pg/mL$ and $7,286.1pg/mL{\pm}5,188.7pg/mL$, p = 0.027). In patients with overweight, the fatigue score was significantly decreased in the KRG group ($35.0{\pm}13.2$ and $24.5{\pm}8.9$, p = 0.019). Conclusion: Our results show that KRG might be effective in reducing proinflammatory cytokine and fatigue in overweight patients with NAFLD, in addition to improvements in adiponectin levels.

• 생명과학회지
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• 제30권11호
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• pp.1012-1020
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• 2020

생쥐의 가변부위가 인간의 정상부위에 연결되어 제조된 바이오시밀러 자연항체치료제인 레미케이드는 암괴사인자-알파(TNF-α)에 특이적인 항체로써 카이메릭 단일클론항체이며 류마티스 관절염치료를 위해 개발되었다. 바이오시밀러 레미케이드 항체의 생물학적 기능을 연구하기 위해 우리는 단백질 데이터 은행을 이용한 생물정보학 분석을 수행하여 레미케이드 자연항체와 암괴사인자-알파 항원간의 결합기작특징을 분석하였다. 자연항체를 생산하는 세포의 유전적 불안정성 때문에 레미케이드 항체생산이 제한되므로 우리는 중 사슬 가변부위를 다중펩타이드 링커에 의해 경 사슬 가변부위에 연결된 레미케이드 ScFv항체(Remicade)를 제조하였다. 더욱이 더 높은 생산과 더 높은 항원결합력을 위해 레미케이드 ScFv를 leucine zipper에 융합시켰다. Remicade와 RemicadeScZip ScFv는 대장균에서 발현되었고 Ni⁺-NTA-아가로스 컬럼으로 정제하였다. 정제된 단백질들은 예상한대로 sodium dodecyl sulfate-polyacrylamide electrophoresis에서 28.80 kDa과 33.96 kDa을 나타내었다. Remicade는 ELISA, western blot에서 TNF-α 항원에 대한 결합력이 관찰되지 않았으나 RemicadeScZip은 항원결합력을 나타내었다. 추가적인 BLI분석으로 RemicadeScZip의 TNF-α 항원에 대한 결합력을 재확인시켜주었으며 이 결과는 Leucine zipper가 레미케이드 ScFv의 접힘을 안정화시키고 TNF-α 항원에 대한 결합력을 개선시켰음을 제시해주고 있다.

• Journal of Applied Biological Chemistry
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• 제59권4호
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• pp.365-372
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• 2016

본 연구에서는 150 mM HCl/60 % ethanol로 급성 위염을 유발한 마우스에서 증숙 시간에 따른 홍삼의 위염 보효 효과에 대해 살펴보고자 하였다. 백삼과 홍삼의 증숙 시간에 따른 성분을 분석한 결과 사포닌, total polyphenol과 total flavonoid의 총 함량이 증숙 시간에 따라 증가하였고 6시간 증숙한 홍삼에서 가장 높은 함량을 보였다. 또한 1,1-diphenyl-2-picrylhydrazyl와 2,2'-azinobis-3-ethyl-benzothiazoline-6-sulfonic acid radical 소거능 실험을 통해 항산화 활성을 측정한 결과 RG 6에서 가장 높은 활성을 나타냈다. In vitro 실험 결과를 바탕으로 시료를 선택하였고 in vivo 실험을 진행하였다. 급성 위염 마우스 모델에 백삼과 6시간 증숙한 홍삼을 투여하였을 때, RG 6에서 위 점막 손상의 개선을 육안적으로 확인할 수 있었으며, 혈액에서 측정한 ROS 수치도 대조군에 비해 유의적인 감소를 보였다. 또한 염증성 사이토카인을 확인한 결과 대조군에 비해 RG6에서 감소하는 경향을 보였다. 이러한 결과들을 종합해 볼 때 증숙 시간에 따른 홍삼은 급성 위염 유발 마우스 모델에서 위염 보호 효과가 있는 것으로 사료된다.

• Journal of Ginseng Research
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• 제39권2호
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• pp.162-168
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• 2015

Background: Although the aerial parts of hydroponic Panax ginseng are reported to contain higher contents of total ginsenosides than those of roots, the isolation and identification of active metabolites from the aerial parts of hydroponic P. ginseng have not been carried out so far. Methods: The aerial parts of hydroponic P. ginseng were applied on repeated silica gel and octadecylsilane columns to yield four glycosyl glycerides (Compounds 1-4), which were identified based on nuclear magnetic resonance, infrared, fast atom bombardment mass spectrometry, and gas chromatography/mass spectrometry data. Compounds 1-4 were evaluated for inhibition activity on NO production in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. Results and conclusion: The glycosyl glycerides were identified to be (2S)-1-O-7(Z),10(Z),13(Z)-hexadecatrienoyl-3-O-${\beta}$-$\small{D}$-galactopyranosyl-sn-glycerol (1), (2S)-1-O-linolenoyl-3-O-${\beta}$-$\small{D}$-galactopyranosyl-sn-glycerol (2), (2S)-1-O-linolenoyl-2-O-linolenoyl-3-O-${\beta}$-$\small{D}$-galactopyranosyl-sn-glycerol (3), and 2(S)-1-O-linoleoyl-2-O-linoleoyl-3-O-${\beta}$-$\small{D}$-galactopyranosyl-sn-glycerol (4). Compounds 1 and 2 showed moderate inhibition activity on NO production in LPS-stimulated RAW264.7 cells [half maximal inhibitory concentration ($IC_{50}$): $63.8{\pm}6.4{\mu}M$ and $59.4{\pm}6.8{\mu}M$, respectively] without cytotoxicity at concentrations < $100{\mu}M$, whereas Compounds 3 and 4 showed good inhibition effect ($IC_{50}$: $7.7{\pm}0.6{\mu}M$ and $8.0{\pm}0.9{\mu}M$, respectively) without cytotoxicity at concentrations < $20{\mu}M$. All isolated compounds showed reduced messenger RNA (mRNA) expression of interleukin-$1{\beta}$ (IL-$1{\beta}$), IL-6, and tumor necrosis factor-${\alpha}$ in LPS-induced macrophage cells with strong inhibition of mRNA activity observed for Compounds 3 and 4.

• Journal of Ginseng Research
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• 제38권3호
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• pp.167-172
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• 2014

Background: Roles of immune reaction and toll-like receptor-4 (TLR-4) have widely been established in the pathogenesis of alcoholic liver disease (ALD). Methods: We evaluated the biologic efficacy of Korean Red Ginseng (KRG), urushiol, and probiotics (Lactobacillus rhamnosus R0011 and Lactobacillus acidophilus R0052) in mouse models of ALD. Sixty C57BL/6 mice were equally divided into six feeding groups for 10 weeks: normal diet, alcohol, control, alcohol + KRG, alcohol + urushiol, and alcohol + probiotics. Alcohol was administered via a LiebereDeCarli liquid diet containing 10% alcohol. TLR-4 expression, proinflammatory cytokines, and histology, as well as the results of liver function tests were evaluated and compared. Results: No between-group differences were observed with regard to liver function. TLR-4 levels were significantly lower in the KRG, urushiol, and probiotics groups than in the alcohol group ($0.37{\pm}0.06ng/mL$, $0.39{\pm}0.12ng/mL$, and $0.33{\pm}0.07ng/mL$, respectively, vs. $0.88{\pm}0.31ng/mL$; p < 0.05). Interleukin-$1{\beta}$ levels in liver tissues were decreased among the probiotics and KRG groups. The tumor necrosis factor-${\alpha}$ level of liver tissue was decreased in the KRG group. Conclusion: The pathological findings showed that alcohol-induced steatosis was significantly reduced by KRG and urushiol. As these agents improve immunologic capacity, they may be considered in potential anti-ALD treatments.