• 동의생리병리학회지
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• 제19권1호
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• pp.196-203
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• 2005

Gunggui-tang has been used for the therapy of blood disorders in Hangbang medicine for long time. Also, Glycyrrhiza uralensis has been used for deficientblood patterns with an irregular pulse or palpitations, coughing and wheezing, and heat or cold in the lungs. Melanogenesis is a physiological process resulting in the synthesis of melanin pigments. We investigated whether the water extract of Gunggui-tang plus G. uralensis inhibited melanogenesis in B16 melanoma cells. Because the molecular events connecting the regulation in tyrosinase activity remain to be elucidated, we also aimed to determine whether Gunggui-tang gamibang(GTG) affects tyrosinase at the gene activation level in the cells. First, we showed that GTG inhibited the tyrosinase promoter activity and further, down-regulated the tyrosinase protein activity in ${\alpha}-melanocyte-stimulating$ hormone $({\alpha}-MSH)-treated$ B16 melanoma cells. GTG also resulted in a decrease of melanin content in MSH-induced melanogenesis, indicating that GTG may be a useful drug in studying the regulation of melanogenesis. The pretreatment of GTG significantly prevented phosphotransferase activity of c-Jun N-terminal kinase (JNK1) and transcriptional activation of activating protein-1 (AP-1) in MSH-treated B16 melanoma cells. These findings indicate that GTG inhibits melanogenesis of B16 melanoma cells via suppression of phosphotransferase activity of JNK1 and transcriptional activation of AP-1.

• 동의생리병리학회지
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• 제24권5호
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• pp.831-836
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• 2010

In addition to spice, black pepper (Piper nigrum Linne : PnL) has been used as herbal medicine because of its function in anti-oxidation, anti-inflammation, and anti-carcinogenesis. Recently, it has been reported that piperine, a component of PnL, inhibits adipocyte differentiation by repressing various adipogenic gene expressions. In this study, we determined whether piperine is a major constituent of PnL that confers the anti-adipogenic activity at whole genome level. Differentiation of 3T3-L1 pre-adipocytes was induced in presence of PnL extract or piperine. To compare genes that are regulated by PnL extract or piperine, we performed expression profiling using microarrays (Agilent Mouse 44k 4plex). RNA samples were labeled with Cy3 and Cy5, respectively. Labeled samples were hybridized to the microarrays. Results were filtered and cut off set p<0.05. Genes exhibiting significant differences in expression level were classified into Gene Ontology (GO)-based functional categories (http://www.geneontology.org) and KEGG (http://www.genome.jp/kegg/). Extract of PnL and its component piperine reduced lipid accumulation in 3T3-L1 cells during adipogenesis. Such anti-adipogenic activity appears to result from down-regulation of transcription factor genes involved in adipogenesis, and other genes involved in fatty acid synthesis, transport, triglyceride synthesis, and carbohydrate metabolism. These genome-wide studies lead to conclude that piperine, as a critical component of PnL, plays common role with PnL in anti-adipogenesis.

• 동의생리병리학회지
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• 제32권3호
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• pp.157-164
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• 2018

This study was designed to investigate the mechanism of the synergistic anticancer effect of Astragalus membranaceus (AM) and Adenophora triphylla var. japonica (AT) in H1299 human lung carcinoma cells. A combined treatment of ethanol extract of AM (EAM) and AT (EAT) explosively increased the reactive oxygen species (ROS) generation in H1299 cells compared to the single treatment of each of them. Co-treatment of N-acetyl-L-cysteine (NAC) with EAM and EAT markedly enhanced the cell viability and suppressed apoptosis in H1299 cells, suggesting that ROS generation contributed to the anticancer effect of EAM and EAT. Interestingly, the combined treatment of EAM and EAT down-regulated p-AKT in H1299 cells, which was abrogated by NAC treatment. These results clearly indicated that ROS generation mediated the inactivation of AKT. Co-treatment of LY294002 with EAM and EAT significantly reduced the cell viability at a concentration which EAM and EAT didn't show any cytotoxicity. In addition, the recovery of cell viability by co-treatment of NAC with EAM and EAT was quite reversed by LY294002 treatment, which confirmed that the inactivation of AKT played a pivotal role in ROS-mediated apoptosis. Taken together, our results demonstrated that the synergistic anticancer effect of EAM and EAT was mediated by ROS generation and inactivation of AKT. We provide a valuable preclinical data for the development of more effective combination of AM and AT to treat lung cancer.

• 한국가금학회:학술대회논문집
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• 한국가금학회 2004년도 제21차 정기총회 및 학술발표회
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• pp.16-18
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• 2004

본 연구는 닭의 여러 조직별 세포들의 telomere 함유율과 telomerase 활성도를 분석 제시하고자 하였다. 한국재래계의 수정란 및 발생단계별 신생 조직과 출생 후 성장단계별 각 조직들에 대한 telomere의 함량과 telomerase 활성도를 분석하였고, 초기배자, 간, 뇌, 신장, 심장, 생식선 조직 및 백혈구 세포를 분석대상으로 하였다. Telomere의 함량 분석은 chicken telomeric DNA probe를 이용한 Q-FISH법으로 수행하였고, telomerase activity의 분석은 TRAP법을 이용하였다. 분석결과 초기 배자, 생식선 세포 및 신장세포에서는 지속적으로 매우 높은 telomerase activity를 나타내었으나 뇌, 심장, 간 등에서는 발생 및 발육이 진행됨에 따라 유의적 감소 양상을 보였다. 닭의 각 조직별 telomere의 함량 분석결과, 대부분의 세포들이 성장이 진행됨에 따라 telomere 함유율이 감소되는 양상을 보였다. 이상의 결과로부터 telomerase의 활성도와 telomere의 함량간에 매우 밀접한 연관성을 보이며. 이들이 닭 조직별 세포의 분화 및 증식성 특이성과도 밀접한 관련이 있는 것으로 나타났다.

• Biomolecules & Therapeutics
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• 제24권3호
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• pp.338-345
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• 2016

Neurodegenerative diseases are often associated with oxidative damage in neuronal cells. This study was conducted to investigate the neuro-protective effect of methanolic (MeOH) extract of Perilla frutescens var. japonica and its one of the major compounds, rosmarinic acid, under oxidative stress induced by hydrogen peroxide ($H_2O_2$) in C6 glial cells. Exposure of C6 glial cells to $H_2O_2$ enhanced oxidative damage as measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and thiobarbituric acid-reactive substance assays. The MeOH extract and rosmarinic acid prevented oxidative stress by increasing cell viability and inhibiting cellular lipid peroxidation. In addition, the MeOH extract and rosmarinic acid reduced $H_2O_2-indcued$ expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) at the transcriptional level. Moreover, iNOS and COX-2 protein expression was down-regulated in $H_2O_2-indcued$ C6 glial cells treated with the MeOH extract and rosmarinic acid. These findings suggest that P. frutescens var. japonica and rosmarinic acid could prevent the progression of neurodegenerative diseases through attenuation of neuronal oxidative stress.

• Plant Biotechnology Reports
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• 제3권1호
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• pp.75-85
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• 2009

We report here a first evaluation of chilling-responsive gene regulation in the sweetpotato. The growth of sweetpotato plants was severely retarded at $12^{\circ}C$; the lengths of the leaf, petiole, and root were markedly reduced and microscopic observation revealed that the elongation growth of the epidermal cells in each of these organs was significantly reduced. We examined the transcriptional regulation of three sweetpotato expansin genes (IbEXP1, IbEXP2 and IbEXPL1) in response to various chilling temperatures (12, 16, 22, and $28^{\circ}C$). In the leaf and petiole, the highest transcript levels were those of IbEXP1 at $28^{\circ}C$, whereas IbEXPL1 transcript levels were highest in the root. IbEXP1 mRNA levels in the $12^{\circ}C-treated$ petiole showed a fluctuating pattern (transient decrease-recovery-stable decrease) for 48 h. In the leaf and petiole, IbEXP1 and IbEXPL1 exhibited a similar response to chilling in that their mRNA levels decreased at $22^{\circ}C$, increased at $16^{\circ}C$, and decreased dramatically at $12^{\circ}C$. In contrast, mRNA levels of IbEXP2 in the leaf fell gradually as the temperature fell from 28 to $12^{\circ}C$, while they remained unaltered in the petiole. In the root, mRNA levels of IbEXPL1 and IbEXP1 reached maximum levels at $16^{\circ}C$, and decreased significantly at $12^{\circ}C$. These data demonstrated that expression of these three expansin genes was ultimately down-regulated at $12^{\circ}C$; however, transcriptional regulation of each expansin gene exhibited its own distinctive pattern in response to various chilling temperatures.

• Molecular & Cellular Toxicology
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• 제4권2호
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• pp.113-123
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• 2008

Microglia, which is the primary immune effector cells in the central nervous system, constitutes the first line of defense against infection and injury in the brain. The goal of this study was to determine the protective (anti-inflammation) mechanisms of forsythia suspense (FS) on LPS-induced activation of BV-2 microglial cells. The effects of FS on gene expression profiles in activated BV-2 microglial cells were evaluated using microarray analysis. BV-2 microglial cells were cultured in a 100mm dish $(1{\times}10^7/dish)$ for 24hr and then pretreated with $1{\mu}g/mL$ FS or left untreated for 30 min. Next, $1{\mu}g/mL$ LPS was added to the samples and the cells were reincubated at $37^{\circ}C$ for 30 min, 1hr, and 3hr. The gene expression profiles of the BV-2 microglial cells varied depending on the FS. The oligonucleotide microarray analysis revealed that MAPK pathway-related genes such as Mitogen activated protein kinase 1 (Mapk1), RAS protein activator like 2 (Rasal2), and G-protein coupled receptor 12 (Gpr12) and nitric oxide biosynthesis-related genes such as nitric oxide synthase 1 (neuronal) adaptor protein (Nos1ap), and dimethylarginine dimethylaminohydrolase 1 (Ddah1) were down regulated in FS-treated BV-2 microglial cells. FS can affect the MAPK pathway and nitric oxide biosynthesis in BV-2 microglial cells.

• Biomolecules & Therapeutics
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• 제18권4호
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• pp.463-468
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• 2010

T-cell activation depends on signals received by the T-cell receptor and CD28 co-stimulatory receptor. Since B7.1 and B7.2 molecules expressed on the surface of antigen presenting cells provide co-stimulatory signals through CD28 to T-cells, an inhibitor of CD28-B7.1/B7.2 binding has been proposed as a therapeutic agent for suppression of excessive T-cell activity. Although anti-B7.1/B7.2 antibodies are known to block B7.1 and B7.2 molecules, their effects on intracellular events in antigen presenting cells remain unclear. In this study, anti-B7.1/B7.2 antibodies decreased secretion of nitric oxide and pro-inflammatory cytokines such as TNF-$\alpha$, IL-$1{\beta}$, and IL-12 in LPS-activated RAW264.7 macrophage-like cells and peritoneal macrophages. Moreover, anti-B7.1/B7.2 antibodies inhibited $I{\kappa}B{\alpha}$ phosphorylation and down-regulated expression of co-stimulatory molecules including B7.1, B7.2, and PD-L1 in LPS-stimulated peritoneal macrophages. These findings suggest that CTLA4-Ig and anti-B7.1/B7.2 antibodies may be candidates to treat chronic inflammatory diseases and autoimmune responses caused by excessive activation of both T-cells and macrophages.

• 대한한방부인과학회지
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• 제21권1호
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• pp.39-54
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• 2008

Purpose: The purpose of this study was to investigate the anti-inflammatory effects of the water extract of Omisodokeum (OMSDE) on peritoneal macrophages, Methods: To verify the anti-inflammatory mechanism of OMSDE, the activation of nuclear $factor-{\kappa}B$ $(NF-{\kappa}B)$ and the phosphorylation of MAPK were examined. Results: The extract of OMSDE suppressed the production of LPS-induced nitric oxide (NO), tumor necrosis factor $(TNF)-{\alpha}$, interleukin $(IL)-1{\beta}$, IL-6 and IL-12 in the macrophages. OMSDE inhibited the degradation of inhibitory ${\kappa}B-{\alpha}$ $(I{\kappa}B-{\alpha})$ and it suppressed the activation of extracellular signal-regulated kinase (ERK 1/2) but didn't inhibit c-Jun N-terminal kinase (JNK) and p38, indicating that OMSDE may inhibit the pro-inflammatory cytokine production process by inhibiting the activation of $NF-{\kappa}B$ and ERK 1/2. Furthermore, OMSDE inhibited the production of interferon $(IFN)-{\beta}$ but didn't inhibit of $IFN-{\alpha}$ in the LPS-stimulated macrophages through the down-regulation of interferon regulatory factor (IRF)-1 and IRF-7. The Oral administration of OMSDE inhibited LPS-induced endotoxin shock and the production of $TNF-{\alpha}$ in serum but didn't inhibit of $IL-1{\beta}$ and IL-6. Conclusion: These results suggest that OMSDE may be effective in the prevention and treatment of inflammatory diseases.

• Nutrition Research and Practice
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• 제9권1호
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• pp.3-10
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• 2015

BACKGROUND/OBJECTIVES: Inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis, involves chronic inflammation of the gastrointestinal tract. Previously, Sasa quelpaertensis leaves have been shown to mediate anti-inflammation and anti-cancer effects, although it remains unclear whether Sasa leaves are able to attenuate inflammation-related intestinal diseases. Therefore, the aim of this study was to investigate the anti-inflammatory effects of Sasa quelpaertensis leaf extract (SQE) using an in vitro co-culture model of the intestinal epithelial environment. MATERIALS/METHODS: An in vitro co-culture system was established that consisted of intestinal epithelial Caco-2 cells and RAW 264.7 macrophages. Treatment with lipopolysaccharide (LPS) was used to induce inflammation. RESULTS: Treatment with SQE significantly suppressed the secretion of LPS-induced nitric oxide (NO), prostaglandin $E_2$ ($PGE_2$), IL-6, and IL-$1{\beta}$ in co-cultured RAW 264.7 macrophages. In addition, expressions of inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2, and tumor necrosis factor (TNF)-${\alpha}$ were down-regulated in response to inhibition of $I{\kappa}B{\alpha}$ phosphorylation by SQE. Compared with two bioactive compounds that have previously been identified in SQE, tricin and P-coumaric acid, SQE exhibited the most effective anti-inflammatory properties. CONCLUSIONS: SQE exhibited intestinal anti-inflammatory activity by inhibiting various inflammatory mediators mediated through nuclear transcription factor kappa-B (NF-kB) activation. Thus, SQE has the potential to ameliorate inflammation-related diseases, including IBD, by limiting excessive production of pro-inflammatory mediators.