• 대한한방소아과학회지
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• 제26권1호
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• pp.1-15
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• 2012

$CheongGiGeoYangTang$ has been used for anti-allergenic purpose. However there was no experimental study about its effect. Therefore, this study was designed to investigate the anti-allergenic effect of $CheongGiGeoYangTang$. Methods Modifiability of RBL-2H3 mast cells' IL-4, IL-13 was analyzed by qRT-PCR and ELISA. Also, the suppressive effect of GATA-1, GATA-2, NF-AT1, NF-AT2, AP-1 and NF-${\kappa}B$ p65 transcription factors was observed by western blotting. OVA-specific IgE, IL-4 and IL-13 production in ovalbumin allergy model was examined as well. Results It was showed that the RBL-2H3 mast cells treated with $CheongGiGeoYangTang$ extract(CGGYT) was significantly suppressed mRNA expression, production of IL-4 and IL-13, and prominently inhibited the expression of transcription factors including GATA-1, GATA-2, NFAT-1, NFAT-2, c-Fos and NF-${\kappa}B$ p65 but not c-Jun. The administration of CGGYT was suppressed the amount of OVA-specific IgE, IL-4 and IL-13 in OVA/alum-sensitized mice. Conclusions We considered CGGYT would regulate the allergic inflammation as inhibition of IL-4 and IL-13 production in activated mast cells and Th2 cells.

• Journal of Applied Biological Chemistry
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• 제58권4호
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• pp.333-338
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• 2015

본 연구에서는 단삼 열수 추출물의 human epidermal melanocye (HEM) 세포에서의 미백활성을 측정하였다. 버섯유래의 tyrosinase 저해능 측정결과 $1,000{\mu}g/mL$의 농도에서 42%의 저해율을 나타내었으며, HEM 세포내의 tyrosinase, 멜라닌 생합성 저해능은 $5{\mu}g/mL$에서 26, 25%의 저해능을 나타내었다. 단삼 추출물의 미백과 관련된 tyrosinase, tyrosinase related protein 1 (TRP-1), tyrosinase related protein 2 (TRP-2), microphthalmia associated transcription factor (MITF)의 단백질 및 유전자 양이 감소함을 나타내었다. 또한 그 상위 단계인 cAMP 발현이 $5{\mu}g/mL$ 농도에서 41% 감소하는 것을 확인하였다. 본 실험을 통하여 단삼 추출물이 cAMP를 효과적으로 억제함으로써, 이를 통해 tyrosinase 활성뿐만 아니라 TRP-1, TRP-2 그리고 MITF 발현을 효과적으로 저해 한다는 사실을 확인하여 기능성 미백 화장품 소재로서의 활용 가능성을 제시하고자 한다.

• The Korean Journal of Physiology and Pharmacology
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• 제17권4호
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• pp.315-320
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• 2013

Here, we show that radicicol, a fungal antibiotic, resulted in marked inhibition of inducible nitric oxide synthase (iNOS) transcription by the pancreatic beta cell line MIN6N8a in response to cytokine mixture (CM: TNF-${\alpha}$, IFN-${\gamma}$, and IL-$1{\beta}$). Treatment of MIN6N8a cells with radicicol inhibited CM-stimulated activation of NF-${\kappa}B$/Rel, which plays a critical role in iNOS transcription, in a dose-related manner. Nitrite production in the presence of PD98059, a specific inhibitor of the extracellular signal-regulated protein kinase-1 and 2 (ERK1/2) pathway, was dramatically diminished, suggesting that the ERK1/2 pathway is involved in CM-induced iNOS expression. In contrast, SB203580, a specific inhibitor of p38, had no effect on nitrite generation. Collectively, this series of experiments indicates that radicicol inhibits iNOS gene expression by blocking ERK1/2 signaling. Due to the critical role that NO release plays in mediating destruction of pancreatic beta cells, the inhibitory effects of radicicol on iNOS expression suggest that radicicol may represent a useful anti-diabetic activity.

• BMB Reports
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• 제53권3호
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• pp.166-171
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• 2020

A chemical library comprising 2,354 drug-like compounds was screened using a transcription and replication-competent viruslike particle (trVLP) system implementing the whole Ebola virus (EBOV) life cycle. Dose-dependent inhibition of Ebola trVLP replication was induced by 15 hit compounds, which primarily target different types of G protein-coupled receptors (GPCRs). Based on the chemical structure, the compounds were divided into three groups, diphenylmethane derivatives, promazine derivatives and chemicals with no conserved skeletons. The third group included sertindole, raloxifene, and ibutamoren showing prominent antiviral effects in cells. They downregulated the expression of viral proteins, including the VP40 matrix protein and the envelope glycoprotein. They also reduced the amount of EBOV-derived tetracistronic minigenome RNA incorporated into progeny trVLPs in the culture supernatant. Particularly, ibutamoren, which is a known agonist of growth hormone secretagogue receptor (GHSR), showed the most promising antiviral activity with a 50% effective concentration of 0.2 μM, a 50% cytotoxic concentration of 42.4 μM, and a selectivity index of 222.8. Here, we suggest a strategy for development of anti-EBOV therapeutics by adopting GHSR agonists as hit compounds.

• Molecular & Cellular Toxicology
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• 제1권2호
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• pp.73-77
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• 2005

Nickel is the one of potent environmental, the occupational pollutants and the classified human carcinogens. It is a serious hazard to human health, when the metal exposure. To prevent human diseases from the heavy metals, it is seemingly important that understanding of how nickel exerts their toxicity and carcinogenic effect at a molecular and a genomic level. The process of nickel absorption has been demonstrated as phagocytosis, iron channel and diffusion. Uptaked nickel has been suggested to induce carcinogenesis via two pathways, a direct DNA damaging pathway and an indirect DNA damaging pathway. The former was originated from the ability of metal to generate Reactive Oxygen Species (ROS) and the reactive intermediates to interact with DNA directly. Ni-generated ROS or Nickel itself, interacts with DNAs and histones to cause DNA damage and chromosomal abnormality. The latter was originated from an indirect DNA damage via inhibition of DNA repair, or condensation and methylation of DNA. Cells have ability to protect from the genotoxic stresses by changing gene expression. Microarray analysis of the cells treated with nickel or nickel compounds, show the specific altered gene expression profile. For example, HIF-I (Hypoxia-Inducible Factor I) and p53 were well known as transcription factors, which are upregulated in response to stress and activated by both soluble and insoluble nickel compounds. The induction of these important transcription factors exert potent selective pressure and leading to cell transformation. Genes of metallothionein and family of heat shock proteins which have been known to play role in protection and damage control, were also induced by nickel treatment. These gene expressions may give us a clue to understand of the carcinogenesis mechanism of nickel. Further discussions on molecular and genomic, are need in order to understand the specific mechanism of nickel toxicity and carcinogenicity.

• Asian-Australasian Journal of Animal Sciences
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• 제19권10호
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• pp.1508-1513
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• 2006

Myostatin (MSTN) and insulin-like growth factors (IGFs) are a known inhibitor and stimulators of proliferation and differentiation of muscle cells, respectively. The present study was performed to investigate the relationship of MSTN-induced growth inhibition to expression of the IGF system components and myogenin, a muscle cell-specific transcription factor, in rat L6 myoblasts. The L6 cells transfected with a green fluorescent protein-MSTN plasmid expression construct had a 47% less cell number than mock-transfected cells after 3-d serum-free culture, accompanied by delayed differentiation which was suggested by inhibited aggregation of cells. Moreover, cells transfected with the expression construct had decreased expression of IGF-II and myogenin genes, but not IGF-I or its receptor genes, as examined by reverse transcription-polymerase chain reaction. The reduced mitosis of the L6 cells transfected with the MSTN-expression construct increased following an addition of either IGF-I or IGF-II to the culture medium, but not to the level of mock-transfected cells. By contrast, myogenin gene expression in these cells increased after the addition of either IGF to the level of mock-transfected cells. Collectively, these results suggest that the inhibitory effect of MSTN on L6 cell proliferation and differentiation is likely to be partly mediated by serially suppressed expression of IGF-II and myogenin genes, not IGF-I gene.

• 치위생과학회지
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• 제15권4호
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• pp.488-494
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• 2015

치주인대세포의 효과적인 조절은 성공적인 치주 조직 재생에 중요한 역할을 한다. NFATc1의 활성화가 골모세포에서 분화를 자극하지만, 치주인대세포가 골모세포로 분화하는 과정에서 NFATc1의 역할은 아직 보고되지 않았다. 본 연구는 hPDLCs가 골모세포로 분화하는 동안 NFATc1의 mRNA의 발현과 단백질 발현이 유도됨을 처음으로 확인하였다. CsA에 의한 NFATc1의 억제는 세포증식을 감소시켰다. 게다가, CsA를 처리한 결과, 분화표지자, ALP activity 및 광화결정형성을 감소시켰다. 이러한 연구 결과는 NFATc1이 치주 재생을 위한 골모세포 분화에 중요한 조절자 역할을 할 수 있을 것으로 생각된다.

• Molecular & Cellular Toxicology
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• 제5권3호
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• pp.230-236
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• 2009

Acrolein, a known toxin in cigarette smoke, is the most abundant electrophilic $\alpha$, $\beta$-unsaturated aldehyde to which humans are exposed in a variety of environmental pollutants, and is also product of lipid peroxidation. Increased unsaturated aldehyde levels and reduced antioxidant status plays a major role in the pathogenesis of various diseases such as diabetes, Alzheimer's and atherosclerosis. The findings reported here show that low concentrations of acrolein induce heme oxygenase-1 (HO-1) expression in RAW 264.7 macrophages. HO-1 induction by acrolein and signal pathways was measured using reverse transcription-polymerase chain reaction, Western blot and immunofluorescence staining analyses. Inhibition of extracellular signal-regulated kinase activity significantly attenuated the induction of HO-1 protein by acrolein, while suppression of Jun N-terminal kinase and p38 activity did not affect induction of HO-1 expression. Moreover, rottlerin, an inhibitor of protein kinase $\delta$, suppressed the upregulation of HO-1 protein production, possibly involving the interaction of NF-E2-related factor 2 (Nrf2), which has a key role as a HO-1 transcription factor. Acrolein elevated the nuclear translocation of Nrf2 in nuclear extraction. The results suggest that RAW 264.7 may protect against acrolein-mediated cellular damage via the upregulation of HO-1, which is an adaptive response to oxidative stress.

• Nutrition Research and Practice
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• 제12권1호
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• pp.3-12
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• 2018

BACKGROUND/OBJECTIVES: Sageretia thea is traditionally used as a medicinal herb to treat various diseases, including skin disorders, in China and Korea. This study evaluated the inhibitory effect of Sageretia thea fruit on melanogenesis and its underlying mechanisms in B16F10 mouse melanoma cells. The active chemical compounds in anti-melanogenesis were determined in Sageretia thea. MATERIALS/METHODS: Solvent fractions from the crude extract were investigated for anti-melanogenic activities. These activities and the mechanism of anti-melanogenesis in B16F10 cells were examined by determining melanin content and tyrosinase activity, and by performing western blotting. RESULTS: The n-hexane fraction of Sageretia thea fruit (HFSF) exhibited significant anti-melanogenic activity among the various solvent fractions without reducing viability of B16F10 cells. The HFSF suppressed the expression of tyrosinase and tyrosinase-related protein 1 (TRP1). The reduction of microphthalmia-associated transcription factor (MITF) expression by the HFSF was mediated by the Akt/glycogen synthase kinase 3 beta ($GSK3{\beta}$) signaling pathway, which promotes the reduction of ${\beta}-catenin$. Treatment with the $GSK3{\beta}$ inhibitor 6-bromoindirubin-3'-oxime (BIO) restored HFSF-induced inhibition of MITF expression. The HFSF bioactive constituents responsible for anti-melanogenic activity were identified by bioassay-guided fractionation and gas chromatography-mass spectrometry analysis as methyl linoleate and methyl linolenate. CONCLUSIONS: These results indicate that HFSF and its constituents, methyl linoleate and methyl linolenate, could be used as whitening agents in cosmetics and have potential for treating hyperpigmentation disorders in the clinic.

• BMB Reports
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• 제41권10호
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• pp.745-750
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• 2008

Selenium, an essential trace element possessing anti-carcinogenic properties, can induce apoptosis in cancer cells. We have previously shown that sodium selenite can induce apoptosis by activating the mitochondrial apoptosis pathway in NB4 cells. However, the detailed mechanism remains unclear. Presently, we demonstrate that p53 contributes to apoptosis by directing signaling at the mitochondria. Immunofluorescent and Western blot procedures revealed selenite-induced p53 translocation to mitochondria. Inhibition of p53 blocked accumulation of reactive oxygen species (ROS) and loss of mitochondrial membrane potential, suggesting that mitochondrial p53 acts as an upstream signal of ROS and activates the mitochondrial apoptosis pathway. Selenite also disrupted cellular calcium ion homeostasis in a ROS-dependent manner and increased mitochondrial calcium ion concentration. p38 kinase mediated phosphorylation and mitochondrial translocation of p53. Taken together, these results indicate that p53 involves selenite-induced NB4 cell apoptosis by translocation to mitochondria and activation mitochondrial apoptosis pathway in a transcription-independent manner.