• 한국식물생명공학회:학술대회논문집
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• 한국식물생명공학회 2004년도 생명공학 실용화를 위한 비젼
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• pp.74-79
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• 2004

Little is known about the effect of epigallocatechin-3 gallate (ESCG), a major constituent of green tea, on the expression of cyclooxygenase (COX)-2. Here, we studied the role of phospholipase D (PLD) isozymes in EGCG-induced COX-2 expression. Stimulation of human astrocytoma cells (U87) with EGCG induced formation of phosphatidylbutanol, a specific product of PLD activity, and synthesis of COX-2protein and its product, prostaglandin $E_2$ ($PGE_2$). Pretreatment of cells with 1-butanol, but not 3-butanol, suppressed EGCG-induced COX-2 expression and $PGE_2$ synthesis. Furthermore, evidence that PLD was involved in EGCG-induced COX-2 expression w3s provided by the observations that COX-2 expression was stimulated by over-expression of PLD1 or PLD2 isozymes and treatment with phosphatidic acid(PA), and that prevention of PA dephosphorylation by 1-propranolol significantly potentiated COX-2expression Induced by EGCG. EGCG induced activation of p38 mitogen-activated protein kinase (p38MAPK), and specific Inhibition of p38 MAPK dramatically abolished EGCG-Induced PLD activation, COX-2 expression, and $PGE_2$ formation. Moreover, protein kinase C (PKC) inhibition suppressed EGCG-induced p38 MAPK activation, COX-2 expression, and $PGE_2$ accumulation. The same pathways as those obtained in the astrocytoma cells were active in primary rat astrocytes, suggesting the relevance of the findings. Collectively, our results demonstrate for the first time that PLD isozymes mediate EGCG-induced COX-2 expression through PKC and p38 in immortalized astroglial line and normal astrocyte cells.

• Journal of Periodontal and Implant Science
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• 제34권2호
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• pp.345-356
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• 2004

The triclosan was shown to have anti-microbial and anti-inflammatory effect with inhibition of inflammatory mediators such as prostaglandin $E_2(PGE_2)$. The purpose of this study was to elucidate whether and how $PGE_2$ could be inhibited by triclosan in human gingival fibroblast. Human gingival fibroblast-1 cells (ATCC CRL2014) were pre-treated for 1 hour with triclosan (0.001 ${\mu}/ml{\sim}10$ ${\mu}/ml$) and then stimulated with $TNF-{\alpha}$ (1.0 ng/ml). $PGE_2$ synthesis was evaluated by ELISA and gene expression of COX-1 and COX-2 was evaluated by RT-PCR after $TNF-{\alpha}$, triclosan, and NS-398 (COX-2 inhibitor, 5, ${\mu}M$) and/ or cycloheximide (protein synthesis inhibitor, 2 ${\mu}g/ml$). Triclosan was cytotoxic to human gingival fibroblasts in the concentration higher than 1.0 ${\mu}g/ml$ for longer than 24 hours in tissue culture. The $PGE_2$ synthesis was inhibited by triclosan in dose-dependent manner. Greater COX-2 mRNA suppression was observed with triclosan (0.1 ${\mu}g/ml$) than with $TNF-{\alpha}$ alone, without change in COX-1 gene expression. Inhibitory effects of triclosan on $PGE_2$ synthesis disappeared in presence of cycloheximide. This study suggests that triclosan inhibit prostaglandin $E_2$ at the level of COX-2 gene regulation and require de novo protein synthesis.

• Bulletin of the Korean Chemical Society
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• 제35권11호
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• pp.3219-3223
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• 2014

Ochnaflavone, a naturally occurring biflavonoid composed of two units of apigenin (5,7,4'-trihydroxyflavone) joined via a C-O-C linkage, was first synthesized and evaluated its inhibitory activity on $PGE_2$ production. Total synthesis was accomplished through modified Ullmann diaryl ether formation as a key step. Coupling reactions of 4'-halogenoflavones and 3'-hydroxy-5,7,4'-trimethoxyflavone were explored in diverse reaction conditions. The reaction of 4'-fluoro-5,7-dimethoxyflavone (2c) and 3'-hydroxy-5,7,4'-trimethoxyflavone (2d) in N,N-dimethylacetamide gave the coupled compound 3 in 58% yield. Synthetic ochnaflavone strongly inhibited PGE2 production ($IC_{50}=1.08{\mu}M$) from LPS-activated RAW 264.7 cells, which was due to reduced expression of COX-2. On the contrary, the inhibition mechanism of wogonin was somewhat different from that of ochnaflavone although wogonin, a natural occurring anti-inflammatory flavonoid, showed strong inhibitory activity of $PGE_2$ production ($IC_{50}=0.52{\mu}M$), and seems to be COX-2 enzyme inhibition. Our concise total synthesis of ochnaflavone enable us to provide sufficient quantities of material for advanced biological studies as well as to efficiently prepare derivatives for structure-activity relationship study.

• 한국한의학연구원논문집
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• 제14권3호
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• pp.57-63
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• 2008

Glehnia littoralis (Umbelliferae) is the medicinal plant used traditionally for treatment of immune-related diseases. Prostaglandins and nitric oxide (NO) have been implicated as important mediators in the processes of inflammation and carcinogenesis. For understanding the mechanisms for pharmacological activities of Glehnia littoralis, we evaluated the inhibitory activity of Glehnia littoralis on lipopolysaccharide (LPS)-induced prostaglandin $E_2$ ($PGE_2$) and NO production in mouse macrophage RAW264.7 cells. The results showed that the extract of Glehnia littoralis inhibited LPS- induced $PGE_2$ production effectively, but not NO. Additional study revealed that the extract of Glehnia littoralis suppressed cyclooxygenase-2 (COX-2) expression in a dose-dependent manner. Present study suggests that Glehnia littoralis may have anti-inflammatory and/or cancer chemopreventive activity through the inhibition of $PGE_2$ production by the suppression of COX-2 activity.

• 한국식품저장유통학회지
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• 제21권1호
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• pp.114-120
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• 2014

LPS로 염증이 유도된 Raw264.7 macrophage에서 대추잎 분획물(Zizyphus jujuba leaf fractions; ZLFs)의 항염증 효과를 살펴 보기위해 세포독성이 나타나지 않은 1, 10, $100{\mu}g/mL$ 농도 범위에서 염증매개물질인 NO, $PGE_2$, 염증성 cytokine(TNF-${\alpha}$, IL-$1{\beta}$ 및 IL-6) 생성 및 COX-2 단백질의 발현을 측정하였다. 그 결과, ZLFs(ZLWF, ZLEF, ZLBF)는 처리 농도 범위에서 효과적으로 NO, $PGE_2$, 염증성 cytokine 생성 및 COX-2 단백질 발현을 억제하였다. 분획 용매에 따른 효과를 살펴보면 ZLWF< ZLBF< ZLEF의 순으로 높은 효과를 나타냈고, 특히 에틸 아세테이트 분획물 ZLEF은 $100{\mu}g/mL$ 처리 농도에서 NO, $PGE_2$, 염증성 cytokine 생성 및 COX-2 단백질 발현 억제 효과가 LPS를 처리하지 않은 음성 대조군보다 우수하거나 비슷하여 본 연구에서 조사된 대추 잎 분획물 중 가장 뛰어난 염증 억제제 후보물질로 확인되었다.

• 한국약용작물학회지
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• 제22권6호
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• pp.457-462
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• 2014

Prostaglandin (PG) $E_2$ is an important mediator of skin wound healing without excessive scarring and gastric ulcer healing. However, $PGE_2$ has a short lifetime in vivo because it is metabolized rapidly by 15-hydroxyprostaglandin dehydrogenase (15-PGDH). Ethanol extract of Eriobotryae folium (EFEE) elevated intracellular and extracellular $PGE_2$ levels in HaCaT cells and inhibited 15-PGDH ($ED_{50}$ : $168.4{\mu}g/mL$) with relatively low cytotoxicity ($IC_{50}$ : $250.0{\mu}g/mL$). Real-time PCR analysis showed that mRNA expression of cyclooxygenase (COX)-1 and COX-2 enzymes were increased and prostaglandin transporter (PGT) was decreased in HaCaT cells by EFEE. Moreover, wound healing effect of EFEE ($168.4{\mu}g/mL$) was comparable to that of TGF-${\beta}1$ (300 pg/mL) as a positive control. These results demonstrate that EFEE may be valuable therapeutic materials for the treatment of $PGE_2$ level dependent diseases.

• Journal of Acupuncture Research
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• 제22권2호
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• pp.147-154
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• 2005

Objective: In this study, the effects of Liriope Platyphylla against LPS-induced inflammation was investigated. Methods: Cell viability was determined using the MTT assay. To identify expressions of COX-2 and iNOS mRNA, RT-PCR was performed. Assessment of PGE2 synthesis was performed using the PGE2 immunoassay. Measurement of NO synthesis was performed using the NO detection. Result : The MTT assay revealed that Liriope Platyphylla exerted no significant cytotoxicity in the microglial BV2 cells. RT-PCR analysis revealed that the mRNA levels of COX-2 and iNOS were significantly decreased in the LPS- and 5 mg/ml Liriope Platyphylla treated group. From the PGE2 immunoassay and NO detection, PGE2 and NO synthesis was significantly suppressed in the LPS- and 5 mg/ml Liriope Platyphylla treated group. Conclusion : In these study, Liriope Platyphylla was shown to suppress PGE2 and NO production by inhibiting LPS-stimulated enhancement of COX-2 enzyme activity and iNOS expression. It is very possible that Liriope Platyphylla can offer a valuable mode of therapy for the treatment of brain inflammatory diseases.

• 한국수산과학회지
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• 제50권1호
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• pp.41-47
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• 2017

Perhaps the most common type of reproductive dysfunction in captive fish is failure of females to undergo final oocyte maturation and thus to ovulate and spawn. The success of aquaculture could therefore be improved by developing techniques to enhance natural spawning, artificial maturation, and/or to induce ovulation in farmed fish. This study aimed to investigate the effects of prostaglandin $E_2$ ($PGE_2$) and prostaglandin $F_{2{\alpha}}$ ($PGF_{2{\alpha}}$) on in vitro oocyte maturation (germinal vesicle breakdown, GVBD) and ovulation in the marine fish Chasmichthys dolichognathus. Post-vitellogenic follicles (0.80-0.94 mm diameter oocytes) were incubated with $PGE_2$ or $PGF_{2{\alpha}}$ at concentrations of 5, 50, or 500 ng/mL for 24 hours. A significant increase in GVBD was seen in 0.84 mm and 0.94 mm oocytes incubated with 50 ng/mL $PGE_2$ compared with the control. There was no significant increase in GVBD in any of the other experimental conditions (5 or 500 ng/mL $PGE_2$ or 5, 50, or 500 ng/mL $PGF_{2{\alpha}}$). Neither of the prostaglandins induced ovulation at the concentrations tested.These results suggest that GVBD was induced by incubation with 50 ng/mL $PGE_2$.

• 한국식품영양과학회지
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• 제35권9호
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• pp.1115-1120
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• 2006

육계 추출물의 대장암 세포에 미치는 영향을 HT-29 인체 결장암 세포주를 이용하여 조사하였다. 육계 추출물은 대장 정상세포인 CCD-112CoN의 성장에는 크게 영향을 미치지 않았으나, 대장암 세포인 HT-29의 성장은 농도, 시간에 의존적으로 크게 억제하였고, 대장암의 진행 과정에서 매우 중요한 COX-2 mRNA 발현량 및 $PGE_2$ 생성, cGMP 생성을 농도 의존적으로 억제하였다. 이상의 결과에서 육계 추출물은 정상세포에는 독성 없이 대장암 세포의 COX-2 및 $PGE_2$, cGMP 생성을 억제함으로써 결과적으로 대장암 세포의 성장을 감소시킨 것으로 판단된다. 따라서 육계는 부작용이 없는 대장암 예방 건강 보조식품으로서 개발 가능성이 있으며, 암세포 사멸에 대한 더욱 정확한 작용기전의 규명과 활성성분의 분리 및 정제, 응용법 등의 연구가 필요할 것으로 사료된다.

• 대한치과교정학회지
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• 제14권2호
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• pp.203-215
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• 1984

This experiment was performed to explore the effect of electric currents and orthodontic forces on bone $PGE_2$ content and orthodontic tooth movement on cats. Stainless steel electrodes were connected a power pack consisting of five miniature batteries, a transistor, and a resistor. The current $(10{\pm}2{\mu}A)$ was provided by a constant source encased in a palatal acrylic plate. In first experiment, the cathode was placed mesial to the right maxillary canine tooth and the anode was positioned distal to the tooth, Sham electrodes were placed new the left cuspid, to serve as control. Nine cats were divided into three groups evenly. Groups of three animals were treated with electric currents only-for 1, 3 and 7 days, respectively. In second experiment, electric currents and the orthodontic forces of about 80 gm were applied to the right maxillary canine, and the orthodontic forces only were applied to the left maxillary canine. 3 groups of three cats each were treated in this experiment-for 1, 3 and 7 days, respectively. Alveolar bone samples were obtained from sites of tension and compression as well as from contralateral sites. Bone samples were extracted by homogenization in $40\%$ ethanal. The supernatant partitioned twice with 2 volumes of petroleum ether to remove neutral lipids and the aqueous supernatant partitioned in ethyl acetate. After drying the solvent, $PGE_2$ was measured by radioimmunoassay technique. The obtained results were as follows. 1. Teeth treated with combined force and electricity moved faster than those treated with force alone. 2. Alveolar bone $PGE_2$ content of electric stimulation was increased at both electrodes. 3. Alveolar bone $PGE_2$ content of mechanical stimulation at compression sites was gradually increased at all time period. At tension site, $PGE_2$ content increased after 1 day of mechanical stimulation remained elevated at all time period. 4. Alveolar bone $PGE_2$ content of compression sites was increased more than that of tension sites from mechanical stimulation as well as electrical stimulation.