• YAKHAK HOEJI
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• v.44 no.3
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• pp.272-278
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• 2000

The antiinflammatory mechanism of NSAIDs is attributed to the reduction of prostaglandin synthesis by the direct inhibition of cyclooxygenase. Inhibition of prostaglandin production in organs such as stomach and kidney can result in gastric lesions, nephrotoxicity and increased bleeding. In this study, newly designed COX-2 inhibitors, synthesized 1,2-benzothiazine derivatives, were screened in vitro for selectivity of COX-1 and COX-2 inhibition properties. Lead compounds in the structure-activity relationship were studied to synthesize new highly selective COX-2 inhibitors.13 determine inhibitory effect of COX-2, synthesized 1,2-benzothiazine derivatives were screened with accumulation of prostaglandin by lipopolysaccharide (LPS) in aspirin-treated macrophages and murine macropharge cell. Some of synthesized 1,2-benzothiazine derivatives were shown to be effective as selective COX-2 inhibitory activity. Others exhibited a preferential inhibition of COX-2, although some COX-1 inhibitory activity was still present. As a conclusion, simple monomer derivatives were more active than dimer derivatives. Substitution of halogen (Br, C1) on the benzothiazine nucleus slightly enhanced inhibition activity.

• Journal of Applied Biological Chemistry
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• v.66
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• pp.114-121
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• 2023

Selective cyclooxygenase (COX)-2 inhibition is a novel strategy to reduce the risk of gastrointestinal side effects caused by conventional nonsteroidal anti-inflammatory drugs. However, some selective COX-2 inhibitors have become apparent to increase the risk of severe cardiovascular disease. The aim of this study was to examine the anti-inflammatory effect of rosemary extract (RE) and confirm the safety of cardiovascular side effects. Inhibition of COX enzyme activity was assessed, and the levels of COX-2 and prostaglandin E₂ (PGE₂) and COX-1 and thromboxane B₂ (TXB₂) were evaluated in lipopolysaccharide (LPS)-induced RAW 264.7 cells. The 40% RE group showed increased COX-2 inhibition activity in a dose-dependent manner, whereas the 50% RE group only exhibited at 100 ㎍/mL. In a cell-based study, COX-2 mRNA expression was similar in both RE groups and PGE₂ levels tended to decrease in the 40% RE group compared to the LPS group in the LPS pretreatment condition. In the LPS posttreatment condition, the COX-2 mRNA expression decreased in the 40% RE group, and PGE₂ levels were increased in the 40 and 50% RE groups. In both conditions, there was no significant difference in COX-1 and TXB₂ levels. In conclusion, 40 and 50% RE showed significant COX-2 inhibition, similar to the positive control group. It was confirmed that the inhibition of the COX-2 expression, but the effect did not affect the balance between prostacyclin and TXB₂. These results indicate that rosemary showed COX-2 inhibition activity with a low risk of cardiovascular diseases.

• Proceedings of the PSK Conference
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• 2003.10b
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• pp.94.2-94.2
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• 2003

CJ-11668 is a new potent and selective COX-2 inhibitor. CJ-11668 showed COX-2 inhibition (IC50) of 65nM and selectivity ratio (COX-l/COX-2) of 770 in the cell based assay. In the human whole blood assay, CJ-11668 showed COX-2 inhibition (IC50) of 370nM and selectivity ratio (COX-l/COX-2), 135. The treatment of CJ-11668 (5 mg/kg, p.o) produced a significant inhibition (35%) of inflamed rat paw volume in the carrageenan-induced acute inflammation. CJ-11668 also suppressed the PGE2 level (69% inhibition, 1 mg/kg, p.o) in the zymosan-induced mouse air pouch model after 3 hrs. (omitted)

• 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.

• Proceedings of the PSK Conference
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• 2002.10a
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• pp.244.1-244.1
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• 2002

Cyclooxygenase-2 ( COX-2 ) is an inducible enzyme which produces prostanoids by various stimuli. Overexpression of COX-2 in many tumor types indicates its association with tumor progression, which has been a promising target for chemoprevention and chemomodulation. We studied conc- and time-dependency of COX-2 inhibition, growth inhibition, and cell cycle arrest induced by celecoxib, a selective COX-2 inhibitor, in human non-small cell lung cancer (NSCLC) A549 cells. (omitted)

• Journal of Yeungnam Medical Science
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• v.17 no.1
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• pp.1-11
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• 2000

Inhibition of cyclooxygenase(COX), and thus prevention of the formation of prostaglandins, provided a unifying explanation of the therapeutic and toxic actions of nonsteroidal anti-inflammatory drugs (NSAIDs). Recently, the discovery of the two isoforms of COX was made by molecular biologists studying neoplastic transformation in chick embryo cells. The constitutive enzyme, COX-1, is obviously responsible for the production of prostaglandins involved in housekeeping functions such as maintenance of integrity of the gastric mucosa, renal blood flow and platelet aggregation. The inducible form of COX (COX-2) is responsible for the formation of prostaglandins that pathologically affects inflammation, pain and fever. Clearly, all the experimental and clinical data support the hypothesis that the beneficial effects of NSAIDs are due to inhibition of the COX-2 enzyme, whereas the gastrotoxicity is due to inhibition of COX-1. The cox-2/COX-1 ratios of the NSAIDs in common use have been measured and compared with epidemiological data on their side effects. There is little evidence to suggest that one NSAID is clearly more effective than another, But substantial individual variability is present with respect to the pharmacology and pharmacokinetics of these drugs: therefore it is essential to adjust the dosage and choose specific drug to the patient's response.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.30 no.4
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• pp.333-344
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• 2008

The objectives of this study was to explore the growth pattern of the oral squamous cell carcinoma when overexpressed COX was inhibited, explore the pathway that COX inhibitors suppressed the proliferation of cancer cells, and then hereafter investigate the potential of COX as chemopreventive target for oral squamous cell carcinoma. For confirming the COX-dependent effect and mechanisms on growth of the oral cancer cells, we treated the nonselective NSAID, Mefenamic acid and COX-2 selective inhibitor, Celecoxib in HN4 cell line. And then the cell line was evaluated with MTT assay and growth curve, the production of PGE2, total RNA extraction and RT-PCR analysis, and TEM The results were obtained as follows: 1. After administration of medication, in the result of MTT assay, Celecoxib inoculated group inhibit the cell growth rather than Mefenamic acid inoculated group. 2. The growth curve of cell line showed as time passes by there was a dramatic cell growth in the control group, and gradual growth inhibition was found in medication inoculated group and, in Celecoxib inoculated group there was more inhibition of cell growth. 3. After the administration of medication, Celecoxib tend to inhibit the synthesis of PGE2 more than Mefenamic acid. Mefenamic acid inhibit the synthesis of PGE2 more as the concentration gets high, but Celecoxib inhibited the synthesis of PGE2 even in low concentration. 4. After the administration of medication, the revelation of COX mRNA in cell line, there was a 50% decrease in COX-1, 60% decrease in COX-2 as in $50{\mu}M$ Mefenamic acid, and in Celecoxib $50{\mu}M$ there was not much difference in COX-1 and 90% decrease in COX-2 was found. 5. HN4 cell line showed broken nucleus and tangled cytoskeleton bundles in cytoplasm which meant apoptotic features after the treatment of Celecoxib in TEM view. Depending on the above results, we estimate that the inhibition of the expression of COX-2 cause the growth suppression of the oral squamous cell carcinoma, and it get achieved through pathway of reduced PGE2 production and increased apoptosis. In addition to, because COX-2 selective inhibitor specifically act to COX-2, it is considered that COX-2 selective inhibitor has the adequate potential as chemopreventive agent for oral squamous cell carcinoma.

• Journal of Physiology & Pathology in Korean Medicine
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• v.20 no.2
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• pp.455-459
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• 2006

The inhibitors of prostaglandin $E_2\;(PGE_2)$ production and cyclooxygenase-2 (COX-2) activity have been considered as potential anti-inflammatory agents. In this study, we evaluated 9 compounds isolated from 5 Korean phytomedicinal plants (Spirea prunifolia, Paeonia suffruticosa, Salvia miltiorrhiza, Scutellaria baicalensis, and Artemisia capillaris) for the inhibition of $PGE_2$production and COX-2 expession in lipopolysaccharide (LPS)-stimulated human macrophages U937 cells. As a result, several compound such as prunioside A, penta-O-galloyl-beta-D-glucose, tanshinone IIA, baicalin, baicalein, wogonin, scopolatin, scoparone and decursinol showed potent inhibition of $PGE_2$production (50-70% inhibition at the test concentration of $10\;{\mu}M$). In addition, these compounds were also considered as potential inhibitors of COX-2 activity (45-73% inhibition at the test concentration of $10\;{\mu}M$). These active compound mediating COX-2 inhibitory activities are warranted for further elucidation of active principles for development of anti-inflammatory agents and these properties may contribute to the anti-atopic dermatitis activity.

• Proceedings of the Korean Society of Applied Pharmacology
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• 2001.11a
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• pp.86-86
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• 2001

Based on the potential inhibitors of cyclooxygenase-2 (COX-2) as anti-inflammatory or cancer chemopreventive agents, we have evaluated the active principles of COX-2 inhibition from natural products. The methanol extract of the cortex of Eugenia caryoplyllata (Myrtaceae) showed the potent inhibition of prostaglandin E$_2$(PGE$_2$) production in lipopolysaccharide (LPS)-activated RAW 264.7 cells (98.3% inhibition at the test concentration of 10 $\mu\textrm{g}$/$m\ell$) Further, hexane-soluble layer was the most active partition compared to ethyl acetate, n-butanol, and water -soluble parts. By bioassay-guided fractionation of hexane-soluble layer, eugenol was isolated and exhibited a significant suppression of PGE$_2$ production (IC$\_$50/=0.06$\mu\textrm{g}$/$m\ell$). In addition, eugenol suppressed the COX-2 gene expression in LPS-stimulated mouse macrop-hage cells. Therfore, eugenol might be a plausible lead candidate for further developing the COX-2 inhibitor as an anti-inflammatory or cancer chemopreventive agent.

• Korean Journal of Oriental Medicine
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• v.8 no.1
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• pp.65-74
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• 2002

Inflammation is a disease that continues to afflict large numbers of people and may cause other diseases, for example, rheumatoid arthritis, colon cancer, etc. prostaglandins(PGs), one of arachidonic acid metabolites, are major chemical mediators in the process of inflammation. In traditional herbal medicine, many kinds of herbal drugs have been widely used for the treatment of inflammation. So, we analyzed many publications until 2001 which worked on inhibition of $PGE_2$ synthesis by cyclooxygenase-2 (COX-2) with herbs and herb oriented single compounds. And then we tried to make interpretations of herbal traditional prescriptions for inflammation. There are significant correlations between herbal medicine prescribed and inhibitions of COX-2 activity. From our efforts and further researches, we expect to develop new-inflammatory herbal drugs which have more efficacy and fewer side effects.