• Biomolecules & Therapeutics
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• v.13 no.1
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• pp.13-19
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• 2005

The study was undertaken to determine the antagonism of the AP1700 on the development of nalbuphine-induced tolerance and physical dependence. AP1700 is an oriental drug preparationcomposed of 5 natural products and is known to have antinarcotic action with an oral dose of 250 mg/kg in rats. AP1700 significantly inhibits the development of antinarcotic action with an oral dose of 250 mg/kg in rats. AP1700 significantly inhibits the development of nalbuphine-induced physical dependence but does not the tolerance. Mitogen-activated protein kinase, which include extracellular signal-regulated kinase (ERK), p38 and c-Jun N-terminal kinase (JNK)/stress-activated protein kinase (SAPK) play critical roles in cell growth and survival and drug abuse. The level of pCREB was elevated in the hippocampus by the chronic treatment with nalbuphine, however, the elevation of pCREB was not inhibited by the AP1700 co-treatment. Interestingly, the level of pERK was decreased in the co-treatment with nalbuphine and AP1700 on the cortex and striatum. However, the level of nNOS and NR1 was not modulated by the treatment with nalbuphine or AP1700 on the cortex, hippocampus and striatum in the rat brain. These results suggest that the AP1700 could be used to ameliorate the nalbuphine withdrawal symptoms.

• YAKHAK HOEJI
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• v.60 no.3
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• pp.128-134
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• 2016

L1 cell adhesion molecule (L1CAM) is a cell surface molecule to initiate a variety of cellular responses through interacting with other cell adhesion molecules in a homophilic or heterophilic manner. Although its expression was found to be upregulated in some tumor cells, including cholangiocarcinomas, and ovarian cancers, and many studies have investigated the role of L1CAM in these cancers, its role in inflammatory responses has been poorly understood. In this study, we explored the role of L1CAM in macrophage-mediated inflammatory responses. L1CAM significantly suppressed the production of nitric oxide (NO), but induced cell proliferation in RAW264.7 cells. L1CAM expression was detectable, but its expression was markedly decreased by lipopolysaccharide (LPS) in RAW264.7 cells. In addition, the expression of pro-inflammatory genes, such as tumor necrosis factor (TNF)-${\alpha}$, cyclooxygenase (COX)-2, and inducible nitric oxide synthase (iNOS) induced by LPS was dramatically suppressed by L1CAM in RAW264.7 cells. L1CAM inhibited the transcriptional activities of NF-${\kappa}B$ and AP-1 while its cytoplasmic domain deletion form, $L1{\Delta}CD$ did not suppressed their activities in RAW264.7 cells. Moreover, L1CAM suppressed nuclear translocation of p65 and p50 as well as c-Jun, c-Fos and p-ATF2 which are transcription factors of NF-${\kappa}B$ and AP-1, respectively. In conclusion, L1CAM suppressed inflammatory responses in macrophages through inhibiting NF-${\kappa}B$ and AP-1 pathways.

• Journal of the Society of Cosmetic Scientists of Korea
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• v.30 no.2
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• pp.221-225
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• 2004

The root of Panax ginseng C. A. Meyer has been used as a traditional anti-aging and anti-wrinkle agent in the Orient. However, it is still unknown which component of ginseng is effective at suppressing wrinkle formation. Recently at least twenty ginsenosides regarded as the main active ingredients of ginseng have been isolated. Among them, we examined the effect of ginsenoside Rg3 on dermal ECM metabolism to elucidate the mechanism of anti-wrinkle by ginseng. In our study, to investigate the anti-wrinkle effect of the ginsenoside Rg3, ECM component and growth factor in dennis were evaluated by ELISA assay. Ginsenoside Rg3 was found to stimulate type I procollagen and fibronectin (FN) biosynthesis in a dose-dependent manner in normal human fibroblast culture (p < 0.05, n =3), and dose-dependently enhance TGF- ${\beta}$1 level (p < 0.05, n =3). In RT-PCR analysis mRNA level of c-Jun, a member of AP-1 transcription factor, was reduced by ginsenoside Rg3 in normal human fibroblast culture. These results indicate that ginsenoside Rg3 stimulates type I collagen and FN synthesis through the changes of TGF - ${\beta}$1 and AP-1 expression in fibroblasts.

• BMB Reports
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• v.41 no.4
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• pp.328-333
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• 2008

A variety of anti-inflammatory agents have been shown to exert chemopreventive activity via targeting of transcription factors such as NF-${\kappa}B$ and AP-1. Lithospermum erythrorhizon (LE) has long been used in traditional oriental medicine. In this study, we demonstrated the inhibitory effects of LE extracts on lipopolysaccharide (LPS)-stimulated production of inflammatory cytokines. As an underlying mechanism of inhibition, LE extracts reduced LPS-induced transactivation of AP-1 as well as NF-${\kappa}B$ in mouse macrophage cells. Electrophoretic mobility shift assays indicated that LE extracts inhibited the DNA binding activities of AP-1 and NF-${\kappa}B$. In addition, phosphorylation of $I{\kappa}B-{\alpha}$ protein was suppressed by LE extracts. Moreover, LE extracts inhibited c-Jun N-terminal kinase and extracellular signal-regulated signaling pathways. Our results suggest that the anti-inflammatory activity of LE extracts may be mediated by the inhibition of signal transduction pathways that normally lead to the activation of AP-1and NF-${\kappa}B$. These inhibitory effects may be useful for chemoprevention of cancer or other chronic inflammatory diseases.

• Archives of Pharmacal Research
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• v.26 no.5
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• pp.375-382
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• 2003

Effects of ginsenosides on nitric oxide (NO) production induced by lipopolysaccharide plus TNF-$\alpha$ (LNT) were examined in C6 rat glioma cells. Among several ginsenosides, ginsenoside Rd showed a complete inhibition against LNT-induced NO production. Ginsenoside Rd attenuated LNT-induced increased phosphorylation of ERK. Among several immediate early gene products, only Jun Band Fra-1 protein levels were increased by LNT, and ginsenoside Rd attenuated Jun Band Fra-1 protein levels induced by LNT. Furthermore, LNT increased AP-1 DNA binding activities, which were partially inhibited by ginsenoside Rd. Our results suggest that ginsenoside Rd exerts an inhibitory action against NO production via blocking phosphorylation of ERK, in turn, suppressing immediate early gene products such as Jun Band Fra-1 in C6 glioma cells.

• Korean Journal of Ecology and Environment
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• v.41 no.4
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• pp.554-562
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• 2008

To evaluate the limitation for epiphytic and planktonic algal growth, acid extractable inorganic phosphorus (AP), implying the luxury uptake phosphorus, was measured in five reed zones of Lake Biwa. The AP in epiphytic substances was 0.7 to 1.4 mg P surface stem $m^{-2}$ in summer and 1.2 to 2.8 mg P $m^{-2}$ in winter. On the other hand, the amount in planktonic substances was 1.4 to 5.7 mg P m -3 and 0.8 to 5.4 mg P $m^{-3}$ in both seasons. Contribution of AP in the epiphytic and planktonic phosphorus was 23 to 31% and 8 to 27% in summer, and 17 to 22% and 9 to 17% in winter. It suggests that in summer both epiphytic and planktonic algae had been luxuriously taken up phosphate into cells. The weight ratios of C : N : P were averaged 79 : 20 : 1 for the epiphytic substances and 81 : 12 : 1 for the particulate substances. On the other hand, the ratios without the luxurious phosphorus were 93 : 24 : 1 and 103 : 15 : 1, showing much higher values than the Redfield ratio. High ratio in the epiphytic substances indicates that the phosphorus is the limiting parameter, rather than nitrogen, regulating the growth of epiphytic algal populations.

• Archives of Pharmacal Research
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• v.29 no.3
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• pp.218-223
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• 2006

Erythropoietin (EPO), a hematopoietic factor, is required for normal erythrocyte developments, but it has been demonstrated to have many other functions, and its receptor is localized in other tissues. In the present study, we investigated whether EPO can promote other cell proliferation and possible molecular mechanisms. EPO restored the inhibition of the RAW264.7 and PC12 cell growth by fetal bovine serum (FBS) withdrawal in a dose dependent manner, but not that of other cell types tested. The restoring effect of EPO was completed when the RAW264.7 cells were cultured in the medium containing as low as 3% of FBS, and 10 U/mL EPO could replace FBS. The restoring effect of EPO in the RAW264.7 cells was associated with the increased of c-Fos and c-Jun expression as well as AP-1 activation. These data demonstrate that EPO can stimulate RAW264. 7 cell as well as PC12 cell growth even when the cells were cultured without FBS or in the presence of small amounts of FBS in the medium, and this stimulating effect is associated with the activation of AP-1 transcription factor.

• Nutrition Research and Practice
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• v.10 no.3
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• pp.251-258
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• 2016

BACKGROUND/OBJECTIVES: Several pharmacological properties of red rice extract have been reported including anti-oxidant, anti-tumor, and reduced cancer cell invasion. This study was conducted to evaluate the anti-inflammatory effects of red rice extract on the production of inflammatory mediators in lipopolysaccharide (LPS)-induced Raw 264.7 macrophages. MATERIALS/METHODS: Pro-inflammatory cytokines including tumor necrosis factor-${\alpha}$ and interleukin-6 were determined by ELISA and cyclooxygenase-2 and inducible nitric oxide synthase expression was evaluated using western blot analysis. In addition, the signaling pathway controlling the inflammatory cascade such as nuclear factor kappa B ($NF-{\kappa}B$), activator proteins-1 (AP-1), and mitogen-activated protein kinase (MAPK) was determined. RESULTS: Our results showed that red rice polar extract fraction (RR-P), but not non-polar extract fraction, inhibited interleukin-6, tumor necrosis factor-${\alpha}$, and nitric oxide production in LPS-induced Raw 264.7 cells. RR-P also reduced the expression of inflammatory enzymes, inducible nitric oxide synthase, and cyclooxygenase-2. In addition, activation of AP-1 and $NF-{\kappa}B$ transcription factor in the nucleus was abrogated by RR-P. RR-P inhibited the phosphorylation of extracellular signaling-regulated kinase 1/2, c-Jun NH2-terminal kinase, and p38 MAPK signaling responsible for the expression of inflammatory mediators in LPS-stimulated Raw 264.7 cells. Based on chemical analysis, high amounts of proanthocyanidin and catechins were detected in the RR-P fraction. However, only proanthocyanidin reduced $NF-{\kappa}B$ and AP-1 activation in LPS-activated Raw 264.7 cells. CONCLUSION: These observations suggest that the anti-inflammatory properties of RR-P may stem from the inhibition of pro-inflammatory mediators via suppression of the AP-1, $NF-{\kappa}B$, and MAPKs pathways.

• Journal of Animal Science and Technology
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• v.62 no.3
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• pp.385-395
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• 2020

Polyinosinic:polycytidylic acid (poly[I:C]) can stimulate Toll-like receptor 3 (TLR3) signaling pathways. In this study, DF-1 cells were treated with poly(I:C) at various concentrations and time points to examine the comparative expression patterns of innate immune response genes. The viability of DF-1 cells decreased from 77.41% to 38.68% when cells were treated different dose of poly(I:C) from 0.1 ㎍/mL to 100 ㎍/mL for 24 h respectively. The expressions of TLR3, TLR4, TLR7, TLR15, TLR21, IL1B, and IL10 were increased in dose- and time-dependent manners by poly(I:C) treatment. On the contrary, the expression patterns of interferon regulatory factors 7 (IRF7), Jun proto-oncogene, AP-1 transcription factor subunit (JUN), Nuclear Factor Kappa B Subunit 1 (NF-κB1), and IL8L2 were varied; IRF7 and IL8L2 were increasingly expressed whereas the expressions of JUN and NF-κB1 were decreased in a dose-dependent manner after they were early induced. In time-dependent analysis, IRF7 expression was significantly upregulated from 3 h to 24 h, whereas JUN and NF-κB1 expressions settled down from 6 h to 24 h after poly(I:C) treatment although they were induced at early time from 1 h to 3 h. Poly(I:C) treatment rapidly increased the expression of IL8L2 from 3 h to 6 h with a plateau at 6 h and then the expression of IL8L2 was dramatically decreased until 24 h after poly(I:C) treatment although the expression level was still higher than the non-treated control. These results may provide the basis for understanding host response to viral infection and its mimicry system in chickens.

• Journal of Oral Medicine and Pain
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• v.26 no.2
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• pp.95-105
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• 2001

제 4형 콜라젠을 분해하는 MMP-9은 조직 재생에 중요한 역할을 하기 때문에 주목받아 왔는데, 이전의 문헌들에서 PMA에 의해 이 유전자 발현이 강하게 상승발현된다고 알려져 있다. 비록 MMP-9 발현을 조절하는 PMA의 기전이 잘 밝혀지지는 않았지만, 다른 유전자발현에서의 이 phorbol ester의 효과는 c-raf-1-ERK 신호전달통로의 활성에 관해 연구되어 오고 있다. 하지만 이번 연구에서 저자는 MMP-9 발현에서 PMA의 상승효과에는 대개는 스트레스성 자극과 관련된 JNK1 의존성 신호전달과정이 또한 필요하다는 다른 가능성을 조사하였다. 그 결과 JNK 억제재중 하나인 SP 600125가 UM-SCC-1세포주에서 PMA에 의해 유도된 MMP-9 상승발현을 용량의존적으로 억제하는 것으로 나타났고 72시간동안 전처치를 한 경우에 그의 억제효과가 최대이었다. phorbol ester로 처리한 세포에 GAL4 luciferase reporter와 vector를 주입해서 조사한 결과 PMA가 c-Jun transacting 활성을 상승시켰다. 그뿐 아니라 PMA에 의한 MMP-9 촉진자 활성에는 AP-1 motif가 필요하며 이 motif에 c-Jun이 결합하는 것을 EMSA를 통해 확인하였다. 결론적으로 UM-SCC-1 세포주에서 PMA에 의한 MMP9의 증가된 발현은 이미 밝혀진 ERK 경로뿐 아니라 JNK 경로를 통한 결과임이 밝혀져 이 경로를 차단하는 방법이 또하나의 암치료 방향을 제시해주고 있다.