• YAKHAK HOEJI
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• v.46 no.6
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• pp.375-380
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• 2002

In this study, newly designed COX-2 inhibitors, synthetic derivatives of benzothiazine-3-carboxamide, were screened in vitro for selectivity of COX-1 and COX-2 inhibition properties. 7-Bromo-1,2-benzoisothiazine derivatives were obtained from 4-bromotoluene over the chlorosulfonation, amination and oxidation. And benzothiazine ring was synthesized through Gabriel-Colmann rearrangement reaction. To evaluate inhibitory effect of COX-2, synthetic derivatives of benzothiazine-3-carboxamide were tested with accumulation of prostaglandin by lipopolysaccharide in aspirin-treated murine macropharge cell. Some of the synthesized lead compounds have potentially shown the structure-activity relationship for selectivity of COX-2 inhibition activity.

• The Korean Journal of Physiology and Pharmacology
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• v.10 no.3
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• pp.161-165
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• 2006

NO and cyclooxygenase-2 (COX-2) are contributes to vascular inflammation induced by various stimulation. The mechanism, which explains a linkage between NO and COX-2, could be of importance in promoting pathophysiological conditions of vessel. We investigated the effects of NO donors on the COX-l and COX-2 mRNA/protein expression, as well as the nitrite production in culture medium of vascular smooth muscle cell (VSMC). VSMC was primarily cultured from thoracic aorta of rat. In this experiments, COX-l and COX-2 mRNA/protein expressions were analysed and nitrite productions were investigated using Griess reagent. VSMC did not express COX-2 protein in basal condition (Nonlipopolysaccharide (LPS) stimulated). In LPS-stimulated experiments, after 3 hours of NO donor pretreatment, LPS $10{\mu}g/ml$ was treated for 24 hours. COX-l protein expressions were unchanged by SNP and NOR-3. NOR-3 significantly increased COX-2 mRNA/protein expression under LPS stimulation. In contrast, SNP did not increase COX-2 mRNA/protein expression under LPS stimulation. Nitrite production was higher in NOR-3 treatment than SNP treatment under LPS stimulation. These results suggest that the expression of COX-2 in VSMC is regulated by NOR-3, COX-2 expressions were depending on the types of NO donor and LPS stimulation in VSMC.

• Journal of Yeungnam Medical Science
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• v.23 no.1
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• pp.36-44
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• 2006

Background: There is controversy regarding whether COX-2 specific inhibitors are associated with elevation of blood pressure. We compared the effects of aspirin, indomethacin, and celecoxib for vascular reactivity induced by phenylephrine. We also tested the effects of indomethacin and NO donor on COX-1 and COX-2 protein expression, as well as nitrite production in culture medium of vascular smooth muscle cells. Materials and Methods: In this experiment, we used the isometric tension study for vascular reactivity. After 45 minutes of pretreatment with aspirin, indomethacin, celecoxib, and phenylephrine induced contractions were tested. COX-1 and COX-2 protein expressions were analyzed by Western blot and nitrite production by the Griess reaction. Results: Although celecoxib pretreatment caused enhanced arterial contraction, aspirin pretreatment induced more potent arterial contraction than celecoxib in the isometric tension study of rabbit femoral artery. COX-1 protein expression was unchanged by indomethacin, SNP and NOR-3; COX-2 protein expression was increased by the addition of indomethacin, SNP, and NOR-3. Especially, NOR-3, a NO donor, significantly increased COX-2 protein expression with unstimulated conditions as well as LPS stimulation. Induction of nitrite production was higher with NOR-3 treatment than SNP treatment with LPS stimulation. Conclusion: These results suggest that aspirin caused more potent vascular contraction than celecoxib and indomethacin. COX-2 expression in VSMC depended on the types of NO donor and LPS stimulation.

• YAKHAK HOEJI
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• v.51 no.5
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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.

• Radiation Oncology Journal
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• v.25 no.3
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• pp.145-150
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• 2007

Purpose: To investigate the degree and effect of cyclooxygenase (COX)-2 expression on the survival of patients with glioblastoma multiforme (GM). Materials and Methods: Between 1997 and 2006, thirty consecutive GM patients treated with surgery and postoperative radiotherapy (dose range: $44{\sim}65.1$ Gy, median dose: 61.2 Gy) were included in the study. Three patients were excluded that discontinued radiotherapy before receiving a dose of 40 Gy due to mental deterioration. The expression of the COX-2 protein in surgical specimens was examined by immunohistochemical analysis. Survival analysis and verification were performed with respect to sex, age, performance status, resection extent, radiotherapy dose, and degree of COX-2 expression using the Kaplan-Meier method and the log rank test. Results: The median length of follow-up was 13.3 months (range:$6{\sim}83$ months). Staining for COX-2 was positive in all patient samples. Staining for COX-2 that was positive for over 75% of the tumor cells was found in 24 patients. Staining for COX-2 that was positive in less than 25% of tumor cells was found in 3 patients (10.0%), staining for COX-2 that was positive in 25 to 50% of tumor cells was found in 1 patient (3.3%), staining for COX-2 that was positive in 50 to 75% of tumor cells was found in 2 patients (6.7%) and staining for COX-2 that was positive in 75 to 100% of tumor cells was found in 24 patients (80.0%). The median survival and two-year survival rate were 13.5 months and 17.5%, respectively. The survival rate was influenced significantly by the degree of resection (tumor removal by 50% or more) and radiotherapy dose (59 Gy or greater) (p<0.05). The median survival of patients with staining for COX-2 that was positive in less than 75% of tumor cells and in at least 75% of tumor cells was 15.5 and 13.0 months, respectively (p>0.05), and the two-year survival for these groups was 33.3 and 13.3%, respectively (p>0.05). Conclusion: The absence of a statistical correlation between the degree of COX-2 expression and survival in GM patients, despite the high rate of COX-2 positive tumor cells in the GM patient samples, requires further studies with a larger series to ascertain the prognostic value of the degree of COX-2 expression in GM patients.

• Archives of Pharmacal Research
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• v.22 no.4
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• pp.372-379
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• 1999

A series of disubstituted 4,5-polymethylenepyrazoles were synthesized and evaluated their inhibitory activities against COX-2. Some compounds showed strong (0.3 nM) inhibitory activity on COX-2 and were found somewhat selective (up to 16) on COX-2 over COX-1.

• Journal of the Korean Society of Food Science and Nutrition
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• v.41 no.12
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• pp.1701-1707
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• 2012

3,3'-Diindolylmethane (DIM) is a major in vivo derivative of the putative anticancer agent indole-3-carbinol, which is present in cruciferous vegetables and has been reported to have anti-carcinogenic properties. An abnorrmally elevated level of cyclooxygenase-2 (COX-2) has been implicated in the pathogenesis of carcinogenesis. To investigate the mechanism by which DIM exhibits anti-carcinogenic effects, we investigated the effects of DIM on COX-2 expression in MCF-10A human mammary epithelial cells treated with the tumor promoter 12-O-tetradecanoylphorbol 13-acetate (TPA). DIM inhibited TPA-induced COX-2 expression and suppressed the synthesis of prostaglandin $E_2$, one of the major products of COX-2. Nuclear factor-kappa B ($NF-{\kappa}B$) is a transcription factor known to play a role in regulation of COX-2 expression. Treatment of MCF-10A cells with TPA increased nuclear translocation of phospho-p65, with the maximal levels being reached at 1 hour, while DIM inhibited the TPA-induced nuclear translocation of phospho-p65. Overall, we demonstrated that DIM suppresses phorbol ester-induced $PGE_2$ production and COX-2 expression in MCF-10A cells. The reduction in COX-2 levels by DIM maybe mediated through inhibition of $NF-{\kappa}B$ signaling.

• Proceedings of the Korea Society of Environmental Toocicology Conference
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• 2002.10a
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• pp.173-173
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• 2002

In order to understand the mechanism of action of TCDD, we have examined the effect of COX-inhibitors on cyp1a1 activity. We observed the effect of COX-inhibitor on EROD activity in C57BL/6 mouse in vovo. And we also evaluated the effect of COX-inhibitors on cyp1a1 mRNA, mouse cyp1a1 promoter activity and EROD activity in Hepa cell. When Aspirin were pretreated with 3MC in vivo, the EROD activity that was stimulated by 3MC was inhibited. And Pretreatment of Aspirin, Celecoxib, Nimesulide and other several Cox-inhibitors in vitro, inhibited the TCDD stimulated EROD activity and Luciferase acitivity. In case of cyp1a1 mRNA level, Nimesulide and SB100 were able to decrease cyp1a1 mRNA that was stimulated by TCDD, but other tested COX-inhibitors were not decrease. We don't know this different result exactly. For the action of Cox-inhibitors on the Cyp1a1, it seems to be important to do pretreatment of these chemicals as apposed to TCDD. In this study, thus, we have suggested that COX-inhibitors such as aspirin, celecoxib, Nimesulide and other several Cox-inhibitors decrease the TCDD induced Cyp1a1.

• Journal of fish pathology
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• v.26 no.1
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• pp.19-30
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• 2013

Megalocytivirus is a major fish pathogen in marine aquaculture of Asian countries including Korea. Despite of many species affected by this pathogen, little is known interaction between megalocytivirus and the fish immune system. One of the cyclooxygenase isoforms, named COX-2, is playing an important role in immune regulation, and distinct from COX-1 isoform of constitutive activity. COX-2 enzyme is induced by various inflammatory signals, including injection of lipopolysaccharide or infection by pathogenic agents. We cloned COX-2 gene in rock bream using degenerated primers designed from reported sequences of other fish species in PCR followed with 5'- and 3'-end RACE-PCR. The full length of cDNA of rbCOX2 (rock bream COX-2) gene are 2655 bp and that translates into 609 amino acids. The rbCOX-2 genomic organization are found to span 10 exons separated by 9 introns. We also studied if the experimental infection of rock bream with megalocytivirus could affect the expression of COX-2 gene. When injected with LPS, expression of the COX-2 gene was reached peak level at 1 day post injection and showed 13.10 fold increased level compared with that of control. While, when injected with megalocytivirus, we were not able to find significantly increased COX-2 gene expression different from that of control. Cloned and analyzed COX-2 gene in rock bream will help to understand defence mechanisms in fish after viral infection and will also support the development of the measures for treatment and prevention of viral infection.

• The Korea Journal of Herbology
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• v.27 no.6
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• pp.131-137
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• 2012

Objectives : Cyclooxygenase (COX) plays a central role in the inflammatory cascade by converting arachidonic acid into prostaglandin. COX-2 is typically induced by inflammatory stimuli in the majority of tissues, it is responsible for propagating the inflammatory response and thus, considered as the best target for anti-inflammatory drugs. The present study investigated the modulatory effect of ginsenoside Rg3, a principle active ingredient in Panax ginseng, on COX-2 expression in the brain tissue induced by systemic lipopolysaccharide (LPS) treatment in C57BL/6 mice. Methods : Because systemic LPS treatment induces COX-2 expression immediately in the brain, ginsenoside Rg3 was treated orally with doses of 10, 20, and 30 mg/kg at 1 hour before the LPS (3 mg/kg, i.p.) injection. At 4 hours after the LPS injection, COX-2 mRNA was measured by real-time polymerase chain reaction method, COX-2 protein levels were measured by Western blotting. In addition, COX-2 expressions in brain tissue were observed with immunohistochemistry and double immunofluoresence labeling. Results : Ginsenoside Rg3 (20 and 30 mg/kg) significantly attenuates up-regulation of COX-2 mRNA and protein expression in brain tissue at 4 hours after the LPS injection. Moreover, ginsenoside Rg3 (20 mg/kg) significantly reduced the number of COX-2 positive neurons in the cerebral cortex and amygdala. Conclusion : These results indicate that ginsenoside Rg3 plays a modulatory role in neuroinflammation through the inhibition of COX-2 expression in the brain and suggest that ginsenoside Rg3 and ginseng may be effective on neurodegenerative diseases caused by neuroinflammation.