• 대한의생명과학회지
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• 제20권2호
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• pp.70-76
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• 2014

In this study, we investigated the effect of DMSO, a highly dipolar organic liquid, in collagen ($5{\mu}g/ml$)-stimulated platelet aggregation. DMSO inhibited platelet aggregation at 0.5% by inhibiting production of thromboxane $A_2$ ($TXA_2$) which was associated with blocking cyclooxygenase (COX)-1 activity and $TXA_2$ synthase. In addition, DMSO significantly increased the formation of cyclic adenosine monophosphate (cAMP) from adenosine triphosphate (ATP) and cyclic guanosine monophosphate (cGMP) from guanosine triphosphate (GTP). On the other hand, DMSO (0.1~0.5% concentration) did not affect the LDH release which indicates the cytotoxicity. Based on these results, DMSO has anti-platelet effect by regulation of several platelet signaling pathways, therefore we suggest that DMSO could be a novel strategy on many thrombotic disorders.

• Archives of Pharmacal Research
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• 제25권3호
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• pp.329-335
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• 2002

Previously, several prenylated flavonoids having a C-8 lavandulyl moiety were found to inhibit cyclooxygenase-1 (COX-1) as well as 5-lipoxygenase (5-LOX), and sophoraflavanone G was the most potent inhibitor against these eicosanoid generating enzymes among 19 prenylated flavonoids tested. In this investigation, effects of sophoraflavanone G on COX-2 induction from RAW 264.7 cells and in vivo inflammatory response were studied. Sophoraflavanone G inhibited prostaglandin $E_2{\;}(PGE_2)$ production from lipopolysaccharide (LPS)-treated RAW cells by COX-2 down-regulation at 1-50 uM. Other prenylated flavonoids including kuraridin and sanggenon D also down-regulated COX-2 induction at 10-25 uM, while kurarinone and echinoisoflavanone did not. In addition, sophoraflavanone G showed in vivo anti-inflammatory activity against mouse croton oil-induced ear edema and rat carrageenan paw edema via oral (2-250 mg/kg) or topical administration (10-250 ug/ear). Although the potencies of inhibition were far less than that of a reference drug, prednisolone, this compound showed higher anti-inflammatory activity when applied topically, suggesting a potential use for several eicosanoidrelated skin inflammation such as atopic dermatitis.

• 약학회지
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• 제51권5호
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• pp.313-317
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• 2007

A series of luotonin A homologues and their aza-analogues were prepared and evaluated their inhibitory activities on COX-1 and 2 as well as their selectivities on COX-2. The aza-analogue of dimethylene-bridged homologue of luotonin A, 3,3'-dimethylene-2-(1',8'-naphthyrid-2'-yl)-4(3H)-quinazolinone (2b), exhibited strongest inhibitory activity against COX-1 and COX-2 dependent phase of prostaglandin $D_2$ generation in mouse bone marrow-derived mast cells in a concentration-dependent manner with an $IC_{50}$ of 39.3 and $1.89{\mu}M$, respectively. Selectivity of 2b on COX-2 over COX-1 was 21 which implied 2b can be a potential lead for the development of selective COX-2 inhibitor.

• Journal of Acupuncture Research
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• 제21권6호
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• pp.19-36
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• 2004

Objective : The purpose of this study was to investigate the effect of Bee Venom and Melittin Solution on the lipopolysaccharide(LPS) and sodium nitroprusside(SNP)-induced expression of prostaglandin $E_2(PGE_2)$, cyclooxygenase-2(COX-2), nuclear factor kappa B($NF-{\kappa}B$) and nuclear factor kappa B($NF-{\kappa}B$) dependent luciferase activity in RAW 264.7 cells, a murine macrophage cell line. Methods : The expression of PGE2 was determined by determination of $PEG_2$, COX-2 was by western blotting with corresponding antibodies, $NF-{\kappa}B$ was by gel mobility shift assay method and $NF-{\kappa}B$ dependent luciferase activity was investigated by luciferase assay in RAW 264.7 cells. Results : 1. LPS and SNP-induced expression of $PEG_2$ was significant after 24hour. 2. The 0.5, 1 and $5{\mu}g/mL$ of bee venom and the 5 and $10{\mu}g/mL$ of melittin solution inhibited significantly LPS-induced expression of $PEG_2$ and, the $5{\mu}g/mL$ of bee venom and the 5 and $10{\mu}g/mL$ of melittin solution inhibited significantly SNP-induced expression of $PEG_2$ compared with control, respectively. The 0.5 and $1{\mu}g/mL$ of bee venom could not significantly inhibit SNP-induced expression of $PEG_2$ compared with control. 3. The $5{\mu}g/mL$ of bee venom and the 5 and $10{\mu}g/mL$ of melittin solution inhibited significantly LPS and SNP-induced expression of COX-2 compared with control, respectively. The 0.5 and $1{\mu}g/mL$ of bee venom inclined to decrease LPS and SNP-induced expression of COX-2 compared with control. 4. The 0.5, 1 and $5{\mu}g/mL$ of bee venom and the 5 and $10{\mu}g/mL$ of melittin solution inhibited significantly LPS and SNP-induced expression of $NF-{\kappa}B$ compared with control, respectively. 5. The 0.5, 1 and $5{\mu}g/mL$ of bee venom and the 5 and $10{\mu}g/mL$ of melittin solution inhibited significantly LPS-induced expression of $NF-{\kappa}B$ dependent luciferase activity and the 1 and $5{\mu}g/mL$ of bee venom and the 5 and $10{\mu}g/mL$ of melittin solution inhibited significantly SNP-induced expression of $NF-{\kappa}B$ dependent luciferase activity compared with control, respectively. The $NF-{\kappa}B$ inhibitor also inhibited significantly LPS and SNP-induced expression of $NF-{\kappa}B$ dependent luciferase activity compared with control. 6. The 0.5, 1 and $5{\mu}g/mL$ of bee venom and the 5 and $10{\mu}g/mL$ of melittin solution inhibited significantly LPS + IFN-${\gamma}$, TNF-${\alpha}$ and LPS + TNF-${\alpha}$-induced expression of $NF-{\kappa}B$ dependent luciferase activity compared with control, respectively. The $NF-{\kappa}B$ inhibitor also inhibited significantly LPS and SNP-induced expression of $NF-{\kappa}B$ dependent luciferase activity compared with control. Conclusions : These results suggest the inhibitory action of bee venom and melittin solution on the inflammatory mediators such as $PEG_2$, COX-2 and $NF-{\kappa}B$.

• 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.

• 대한본초학회지
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• 제30권5호
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• pp.51-58
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• 2015

Objectives : This paper aimed to verify the applicability of mixed extract ofAngelica gigasNakai,Cnidium officinaleMakino,Paeoniala ctifloraPall,Rechmannia glutinosaLibosch,Scutellaria baicalensisGeorgi, which were prescribed for improving inflammation in Donguibogam, as the materials for beauty food and functional medicinal herb cosmetics by manufacturing such mixed extract and evaluating the biological activity of the extract.Methods : The mixed medicinal herb water extract(MMW) and ethanol extract(MME) were freeze-dried to be used as the specimen. We performed electron donating ability, lipid acidification inhibitory activity, anti-inflammatory activity against skin flora, MTT assay, NO inhibitory activity and the protein expression inhibitory activity of iNOS and COX-2.Results : For anti-oxidation experimentation, the electron donating abilities of MMW and MME were above 60.0% and 90.0% at 500 μg/ml, respectively. In the inhibition rate of lipid peroxidation, MMW and MME showed 43.1% and 52.1% at 1,000 μg/ml, respectively. As a result of antimicrobial activity, both the MMW and MME showed significant clear zones forPropionibacterium acnesat 4 mg/disc, but did not indicated the clearzones forStaphylococcus aureus, Escherichia coliandStaphylococcus epidermidis. Anti-inflammatory activity by NO assay showed LPS-induced NO was significantly inhibited in a concentration-dependent manner. Also, the expression of iNOS and COX-2 proteins were significantly inhibited following treatment with MMW and MME of 50 μg/ml.Conclusions : Accordingly, it can be concluded that mixed medicinal herb extract has the potential to beused as a functional food and cosmetic material.

• 생명과학회지
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• 제18권2호
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• pp.180-186
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• 2008

이상의 연구 결과에 의하면 U937 세포에서 FSB 및 TFS 모두 2 mg/ml의 농도에서 6시간까지는 세포증식에 아무런 영향을 미치지 못하였고 PMA 처리에 의해서도 세포증식에는 변화가 없었으며, 세포의 형태 및 핵의 형태도 PMA와 FSB 및 TFS의 처리에 의해서 아무런 변화가 나타나지 않았다. 그러나 COX-2의 발현의 정도는 PMA 처리에 의해서 증가하였고, 이렇게 증가한 COX-2는 FSB 및 TFS의 선처리에 의해서 효과적으로 억제되는 것으로 나타났다 또한 COX-2에 의해 생성되어 염증반응을 유발하며 세포분열이나 증식에 영향을 줌으로서 각종 질병의 유발과 진행에 중요한 역할을 하는 것으로 알려져 있는 $PGE_2$의 경우도 PMA처리에 의하여 증가하였으며 FSB 및 TFS 처리에 의해서 강하게 억제되었다. 특히 FSB에 비하여 TFS를 선처리하였을 경우 PMA에 의하여 과발현된 COX-2 및 $PGE_2$ 생성의 억제정도가 더 강하게 나타났다. 이러한 결과는 FSB 및 TFS의 항염증기전 해석을 위한 이해와 향후 지속적인 연구를 위한 귀중한 자료가 될 것으로 사료된다.

• 대한약학회:학술대회논문집
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• 대한약학회 2002년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2
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• pp.343.1-343.1
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• 2002

Nonsteroidal antiinflammatory drugs(NSAIDs) are widely used to treat pain. fever and inflammatory condition. But chronic-disease patients suffer from gastro-intestinal disturbances such as discomfort. nausea. peptic ulcer and severe bleeding because NSAIDs inhibit not only COX-2 associated with anti-inflammatory activity but also COX-1 associated with adverse gastro-intestinal effects. On the basis of this fact. specific COX-2 inhibitors such as celecoxib and rofecoxib are introduced in the drug market. (omitted)

• 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.

• 생약학회지
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• 제34권1호통권132호
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• pp.25-27
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• 2003

In order to clarify the anti-thrombosis activity of rhubarb, we investigated the effect of stilbene derivatives from rhizomes of Rheum undulatun on cyclooxygenase activity. Stilbene derivatives (desoxyrhapontigenin, rhapontigenin, piceatannol) exhibited the inhibitory effects on COX-1, and desoxyrhapontigenin showed inhibitory effect on COX-2. These inhibitory effect may partially contributed to anti-thrombosis activity of rhubarb.