• 한국독성학회:학술대회논문집
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• 한국독성학회 2002년도 Molecular and Cellular Response to Toxic Substances
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• pp.14-40
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• 2002

15-Deoxy- Δ$\^$12,14/-prostaglandin J$_2$ (15-deoxy-PGJ$_2$), a naturally occurring ligand activates the peroxisome proliferator-activated receptor-${\gamma}$ (PPAR-${\gamma}$). Activation of PPAR-y has been found to induce cell differentiation such as adipose cell and macrophage. Here it was investigated whether 15-deoxy-PGJ$_2$ has neuronal cell differentiation and possible underlying molecular mechanisms. Dopaminergic differentiating PC 12 cells treated with 15-deoxy-PGJ$_2$ (0.2 to 1.6 ${\mu}$M) alone showed measurable neurite extension and expression of neurofilament, markers of cell differentiation. However much greater extent of neurite extension and expression of neurofilament was observed in the presence of NGF (50 ng/$m\ell$). In parallel with its increasing effect on the neurite extension and expression of neurofilament, 15-deoxy-PGJ$_2$ enhanced NGF-induced p38 MAP kinase expression and its phosphorylation in addition to the activation of transcription factor AP-1 in a dose dependent manner. Moreover, pretreatment of SD 203580, a specific inhibitor of p38 MAP kinase inhibited the promoting effect of 15-deoxy-PGJ$_2$ (0.8 ${\mu}$M) on NGF-induced neurite extension. This inhibition correlated well with the ability of SB203580 to inhibit the enhancing effect of 15-deoxy-PGJ$_2$ on the expression of p38 MAP kinase and activation of AP-1. The promoting ability of 15-deoxy-PGJ$_2$ did not occur through PPAR-${\gamma}$, as synthetic PPAR-${\gamma}$ agonist and antagonist did not change the neurite promoting effect of 15-deoxy-PGJ$_2$. In addition, contrast to other cells (embryonic midbrain and SK-N-MC cells), PPAR-${\gamma}$ was not expressed in PC-12 cells. Other structure related prostaglandins, PGD$_2$ and PGE$_2$ acting via a cell surface G-protein-coupled receptor (GPCR) did not increase basal or NGF-induced neurite extension. Moreover, GPCR (EP and DP receptor) antagonists did not alter the promoting effect of 15-deoxy-PGJ$_2$ on neurite extension and activation of p38 MAP kinase, suggesting that the promoting effect of 15-deoxy-PGJ$_2$ may not be mediated GPCR. These data demonstrate that activation of p38 MAP kinase in conjunction with AP-1 signal pathway may be important in the promoting activity of 15-deoxy-PGJ$_2$ on the differentiation of PC12 cells.

• 한국미생물·생명공학회지
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• 제50권4호
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• pp.574-583
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• 2022

Ficus vasculosa Wall. ex Miq. (FV) has been used as a herbal medicine in Southeast Asia and its antioxidant activity has been shown in previous studies. However, it has not yet been elucidated whether FV exerts anti-inflammatory effects on activated-macrophages. Thus, we aimed to evaluate the ameliorative property of FV methanol extract (FM) on lipopolysaccharide (LPS)-induced inflammatory responses and the underlying molecular mechanisms in RAW264.7 macrophages. The experimental results indicated that FM decreased the production of inflammatory mediators (NO/PGE2) and the mRNA/protein expression of iNOS and COX-2 in LPS-stimulated RAW264.7 cells. FM also reduced the secretion of interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α and monocyte chemoattractant protein (MCP)-1 in LPS-stimulated RAW264.7 cells. Results also demonstrated that FM improved inflammatory response in LPS-stimulated A549 airway epithelial cells by inhibiting the production of cytokines, such as IL-1β, IL-6 and TNF-α. In addition, FM suppressed MAPK activation and NF-κB nuclear translocation induced by LPS. FM also upregulated the mRNA/protein expression levels of heme oxygenase-1 and the nuclear translocation of nuclear factor erythroid 2-related factor 2 in RAW264.7 cells. In an experimental animal model of LPS-induced acute lung injury, the increased levels of molecules in bronchoalveolar lavage (BAL) fluid were suppressed by FM administration. Collectively, it was founded that FM has anti-inflammatory properties on activated-macrophages by suppressing inflammatory molecules and regulating the activation of MAPK/NF-κB signaling.

• Journal of Nutrition and Health
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• 제56권3호
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• pp.231-246
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• 2023

본 연구에서는 MIA로 골관절염을 유도한 SD 흰쥐에서 인도산 보스웰리아 검레진을 주정 추출 후, 헥산으로 지방 제거 공정을 추가하여 제조한 보스웰리아 검레진 추출물인 FJH-UBS의 항골관절염 효능을 평가하기 위해 실시하였다. FJH-UBS는 40 또는 80 mg/kg BW/day 용량으로 5주간 경구투여하였고, FJH-UBS를 2주간 투여 후 MIA (3 mg/50 µL/rat)를 무릎 관절강 내에 주사하여 골관절염을 유도하였다. MIA 유도 골관절염 동물모델에서 FJH-UBS는 무릎 관절의 부종을 감소시키고 연골의 분해를 억제하였으며, 연골 내 type II collagen과 aggrecan 발현을 증가시켰다. FJH-UBS (80 mg/kg BW/day)는 혈청 내 PGE2, LTB4, IL-1β, 및 IL-6 함량을 감소시켰고, MMP-13 함량을 감소시켰다. FJH-UBS (80 mg/kg BW/day)는 연골 활막 내 iNOS, COX-2, 5-LOX, IL-1β, IL-6 및 TNF-α 발현을 감소시켰고, MMP-2, MMP-9 및 MMP-13 발현을 감소시켰다. 이 결과는 FJH-UBS가 염증매개물질과 염증성 cytokine의 발현감소를 통해 염증 반응을 억제하고, MMPs의 발현을 억제하여 연골 기질의 분해를 억제함으로서 항골관절염 효능을 나타냄을 의미하며 이는 관절 및 연골 건강 개선 기능성 원료로 FJH-UBS의 활용 가능성을 제시한다.

• Journal of Microbiology and Biotechnology
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• 제18권3호
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• pp.523-531
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• 2008

Radiotherapy is currently applied in the treatment of human cancers. We studied whether genistein would enhance the radiosensitivity and explored its precise molecular mechanism in cervical cancer cells. After co-treatment with genistein and irradiation, the viability, cell cycle analysis, and apoptosis signaling cascades were elucidated in CaSki cells. The viability was decreased by co-treatment with genistein and irradiation compared with irradiation treatment alone. Treatment with only ${\gamma}$-irradiation led to cell cycle arrest at the $G_1$ phase. On the other hand, co-treatment with genistein and ${\gamma}$-irradiation caused a decrease in the $G_1$ phase and a concomitant increase up to 56% in the number of $G_2$ phase. In addition, co-treatment increased the expression of p53 and p21, and Cdc2-tyr-15-p, supporting the occurrence of $G_2/M$ arrest. In general, apoptosis signaling cascades were activated by the following events: release of cytochrome c, upregulation of Bax, down regulation of Bcl-2, and activation of caspase-3 and -8 in the treatment of genistein and irradiation. Apparently, co-treatment downregulated the transcripts of E6*I, E6*II, and E7. Genistein also stimulated irradiation-induced intracellular reactive oxygene, species (ROS) production, and co-treatment-induced apoptosis was inhibited by the antioxidant N-acetylcysteine, suggesting that apoptosis has occurred through the increase in ROS by genistein and ${\gamma}$-irradiation in cervical cancer cells. Gamma-irradiation increased cyclooxygenase-1 (COX-2) expression, whereas the combination with genistein and ${\gamma}$-irradiation almost completely prevented irradiation-induced COX-2 expression and $PGE_2$ production. Co-treatment with genistein and ${\gamma}$-irradiation inhibited proliferation through $G_2/M$ arrest and induced apoptosis via ROS modulation in the CaSki cancer cells.

• 한국식품영양과학회지
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• 제44권9호
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• pp.1256-1263
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• 2015

본 연구에서는 유자가 선천성 면역력에 미치는 효과를 알아보기 위하여 유자 30% 주정추출물(CJE)을 사용하였으며 선천성 면역에 중요한 역할을 하는 대식세포를 이용해 실험하였다. CJE는 마우스 대식세포인 RAW264.7에서 $1,000{\mu}g/mL$의 최고 농도까지 세포독성을 보이지 않았고, 전사인자 $NF-{\kappa}B$와 염증성 매개물질인 COX-2, PGE2의 활성 및 발 현 증강에 영향을 미치며, 특히 $300{\mu}g/mL$의 농도에서부터 유의적 차이를 보이는 것으로 확인되었다. 산화질소 생성능과 대식세포에서 분비되는 사이토카인인 $TNF-{\alpha}$, $IL-1{\beta}$의 발현을 대조군에 비해 농도 의존적으로 증가시킨다는 결과를 얻었으나, IL-6에서는 통계적으로 약간의 유의성이 있는 증가를 보였고 IL-10은 정상대조군에 비해 거의 유의적인 차이를 보이지 않았다. CJE는 또한 NK 세포의 활성을 농도 의존적으로 증가시키고 비장세포의 증식능도 농도 의존적으로 증가시킨다는 것을 확인하였다. 이러한 결과로 미루어 보아 CJE는 인체의 대식세포 활성의 증가를 통해 선천성 면역력을 증가시킬 것으로 판단된다.

• 대한한의학방제학회지
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• 제18권1호
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• pp.87-94
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• 2010

Objectives : To provide the information of efficacy for Sagunja-tang (Sijunzi-tang; SG), it was evaluated the anti-inflammatory effect. SG, a widely used herbal formula in tranditional Korean medicine, has been used to treat for the Boki-invigorating. In many studies, plant-derived anti-inflammatory efficacies have been investigated for their potential inhibitory effects on lipopolysaccharide (LPS)-stimulated macrophages. This study was performed to examine the anti-inflammatory effects of SG extract on LPS-stimulated RAW 264.7 cells. Methods : The productions of nitric oxide (NO), prostaglandin (PG)$E_2$, interleukin (IL)-6 and tumor necrosis factor (TNF)-$\alpha$ were examined in a macrophage cell line, RAW 264.7 cells, in the presence of the SG extract. RAW 264.7 cells were incubated with LPS $1\;{\mu}g/mL$ and SG extract for 18 hours. The anti-inflammatory activity of SG was investigated by carrageenin-induced paw edema in rats. The paw volume was measured at 0, 2 and 4 hours following carrageenin-induced paw edema in rats. Results : SG extract showed inhibitory effect on $PGE_2$, IL-6 and TNF-$\alpha$ by LPS-stimulated RAW 264.7 cells. But SG extract was not inhibitory effect on NO by LPS-stimulated RAW 264.7 cells. And administration of SG extract (1 g/kg) showed a reduction in carrageenin-induced paw edema on rats. Conclusions : These results suggest that SG extract has anti-inflammatory activities in vitro and in vivo models.

• 대한화장품학회지
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• 제33권1호
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• pp.53-60
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• 2007

테린 계열의 화합물은 생체 내에 존재하여 여러 가지 효소들의 cofactor로써의 역할을 담당하며, 활성 산소에 대하여 제거 작용을 갖는 비단백질 화합물로서 널리 알려져 있다. 테린 계열의 화합물은 (6R)-5,6,7,8-tetrahydrobiopterin (이하 $6-BH_4$)인 완전히 환원된 형태로 활성을 가지며 공기에 노출되었을 경우 쉽게 산화 형태로 전환된다. $6-BH_4$의 결핍 증상으로서 정신 질환관련된 파킨슨 질환, 알츠하이머 질환, 우울증 등의 증상이 있으며, 피부 질환으로는 백반증이 있다. 최근에는 $6-BH_4$의 멜라닌합성 저해와 관련된 연구가 수행되어지고 있다. 본 연구에서는 $6-BH_4$와 유도체인 (6R)-5-methyl-5,6,7,8-tetrahydrobiopterin (이하 methyl-$BH_4$)의 항산화 효능과 미백 효능 및 자외선 손상 방어 효능에 관한 연구를 수행하였다. 테린 화합물의 DPPH 라디칼소거능 평가 결과 항산화 표준 물질인 quercetin과 유사한 효능을 갖는 항산화 물질임을 확인하였으며, 피부 세포주에서의 세포독성이 없는 안전한 물질임을 확인하였다. 또한 미백 효능을 평가하기 위하여 효소 수준에서의 tyrosinase 활성 저해능과 세포수준에서의 tyrosinase, TRP-1단백질의 발현 저해 효능을 확인하였다. in vivo에서의 미백 효능 평가 결과 역시 증류수 처리군과 비교시 테린 화합물 처리군에서 멜라닌 수치가 감소하는 것을 확인할 수 있었다. 테린 화합물의 또 다른 효능으로서 항산화효능을 기반으로 하는 자외선 손상 방어 효능을 평가한 결과, 자외선에 의해 유도되는 cytokines의 발현양을 감소시켰으며, 멜라닌의 합성을 저해하는 것을 확인할 수 있었다. 이러한 결과들로부터 테린 화합물의 화장료적 특성을 확인할 수 있었다.

• 한국약용작물학회지
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• 제22권6호
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• pp.475-482
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• 2014

This study was indicated to enhance the anti-inflammation activities by the fermentation of the fruits of Aronia melanocarpa (Michx.) Elliott. The extracts by 70% ethanol (EE) showed better biological activities than those by hot water (WE) from campared result of the effect of extraction solvents. Then, the extract from 70% ethanol extraction was further fermented by lactic acid, denoted as FEE. For antioxidant activities, the FEE had showed the highest value as 0.832 of reducing powder, in comparison with those of EE and WE. Cytotoxicity of the water extraction (WE) was measured for 12.06% in addition of $1.0mg/m{\ell}$ of FEE. For anti-inflammation activities, NO production from the macrophage, RAW 264.7 was observed as $7.24{\mu}M$ and $8.52{\mu}M$ from FEE and EE, respectively. Prostaglandin $E_2$ ($PGE_2$) production from human fibroblast cell, CCD-986sk, was also estimated for $152pg/m{\ell}$ in addition of $1.0mg/m{\ell}$ of the FEE. The lowest production of both IL-6 and TNF-${\alpha}$ were $3.5pg/m{\ell}$ and $865.5pg/m{\ell}$, respectively in addition of $1.0mg/m{\ell}$ of the FEE, whereas $74.5pg/m{\ell}$ and $982.4pg/m{\ell}$ in treated with same concenrations of the EE. It was also found that the FEE was higher amounts than other extracts through HPLC analysis of the anthocyanins. These results strongly indicate that fermentation process of the lactic acid could enhance anti-inflammation activities of extracts by increasing the amounts of the anthocyanins, especially cyanidin-galactoside. Our results suggest that the application of the fermentation process for other medicinal herbs can be improved their biological activities.

• 생명과학회지
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• 제18권1호
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• pp.23-29
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• 2008

인삼은 고전적으로 항당뇨 효과가 있는 것으로 보고되고 있다. Insulin-like growth factor (IGF) 역시 당뇨병성 신증의 발병 초기에 중요한 역할을 하는 것으로 알려져 있다. 이에 본 연구에서는 mesangial 세포에서 고포도당에 의한 IGF 분비에 대한 ginsenoside의 차단 효과 및 이와 관련된 신호전달계를 알아보았다. 결과는 다음과 같다. 고포도당에 의해 증가 되었던 IGF-I 및 IGF-II 분비 촉진 작용은 GTS, PD 및 PT 처리 시 차단되었으며, 세포 성장 촉진작용에서도 같은 효과를 볼 수 있었다. 아울러 고포도당에 의한 산화성 스트레스 종가, GSH 감소, AA 방출 증가 작용 및 $PGE_2$ 합성 증가 작용은 GTS 처리시 현저하게 차단되었으며 PD 및 PT 처리 시 역시 억제 되는 것으로 나타났다. 이상의 결과를 볼 때 mesangial 세포에서 ginsenoside는 산화성 스트레스 및 arachidonic acid 활성 경로를 억제하여 고포도당에 의한 IGFs 분비 작용을 차단하는 것으로 나타났다.

• 한국식품영양과학회지
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• 제46권4호
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• pp.409-416
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• 2017

천연물 유래 물질의 항염증 활성에 대한 잠재성을 평가하기 위한 일환으로 오배자에서 분리한 PGG가 LPS로 자극한 마우스 대식세포인 RAW264.7 세포에서 염증반응에 미치는 영향에 대해 평가하고 관련 메커니즘에 대해 검토하였다. PGG는 LPS 자극에 의해 유도된 iNOS 및 COX-2 단백질 발현량을 감소함으로써 NO와 $PGE_2$ 생성을 억제할 뿐만 아니라 IL-6, TNF-${\alpha}$와 같은 pro-inflammatory cytokine의 분비를 억제하였다. 이러한 효과는 전사인자인 NF-${\kappa}B$의 세포질에서 핵으로의 이동을 억제함으로써 나타나는 것으로 판단된다. 이러한 결과로부터 PGG가 염증 반응을 저해하는 효과가 있는 것으로 나타나 향후 염증성 질환을 예방, 개선 및 치료하는 데 유용한 물질로 사용될 가능성이 있을 것으로 생각된다.