• Korean Journal of Pharmacognosy
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• v.31 no.1
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• pp.57-62
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• 2000

By bioassay-guided fractionation followed by chromatographic separation of the MeOH extract of Alpinia Rhizome, five COX-2 inhibitors were isolated and characterized as pinocembrin, galangin 3-methyl ether, galangin, kaempferid, and 5-hydroxy-7-(4'-hydroxy-3'-methoxyphenyl)-1-phenyl-3-heptanone.

• Proceedings of the PSK Conference
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• 2002.10a
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• pp.344.1-344.1
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• 2002

We report the synthesis of several new 3-aminohydantoinyl-1.2-benzothiazine derivatives and propose an another mechanism of the cyclization to the hydantoins for the development candidates of COX-2 inhibitors. 3-Aminohydantoins 3a-d were prepared through cyclization of the condensation products that were formed by heating amino acids and tert-bytyl carbazate in quinoline according to the method of Lalezari. (omitted)

• Proceedings of the PSK Conference
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• 2003.04a
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• pp.250.1-250.1
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• 2003

In this work, we have conducted 3D-QSAR studies on a series of acanthonic acid derivatives that act as COX-2 inhibitors, using two different methods: comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA). CoMFA and CoMSIA analysis of twenty five pimarane analogues produced good models with high predictive abilities. (omitted)

• Proceedings of the PSK Conference
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• 2002.10a
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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)

• YAKHAK HOEJI
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• v.48 no.2
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• pp.141-146
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• 2004

Selective COX-2 inhibitors were expected to retain anti-inflammatory activity by inhibition of prostaglandin production with reduction of gastric and renal side effect associated with non-steroidal anti-inflammatory drugs. This study reported the syntheses of novel 2-thiohydantoin and hydantoin derivatives which have the structure of 5-membered heterocyclic ring substituted with two aryl groups, phenyl group at 5-position and p-sulfamylphenyl or p-methoxyphenyl group at 1-position. These synthetic compounds showed significant COX-2 activities in vitro screening. Among them, 5-phenyl-2-thiohydantoin and hydantoin substituted with benzyl group at 3-position, compounds 5 and 8, could be considered as lead compounds with $IC_{50}$/=13.13∼18.78 $\mu\textrm{g}$/$m\ell$ for the development of COX-2 inhibitors.

• Proceedings of the Korean Society of Applied Pharmacology
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• 2003.11a
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• pp.101-101
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• 2003

Prostaglandins (PGs) and nitric oxide (NO) produced by inducible cyclooygenase (COX-2) and nitric oxide synthase (iNOS), respectively, have been implicated as important mediators in the process of inflammation and carcinogenesis. On this line, the potential COX-2 or iNOS inhibitors have been considered as anti-inflammatory and cancer chemopreventive agents. In our continuing efforts of searching for novel cancer chemopreventive agents from natural products, we isolated natural sesquiterpenoids as potential COX-2 and iNOS inhibitors in cultured lipopolysaccharide (LPS)-activated mouse macrophage RAW 264.7 cells. Alantolactone, a natural eudesmane-type sesquiterpenoid, exhibited a potent inhibition of COX-2 (IC50 = 0.4 $\mu\textrm{g}$/$m\ell$) and iNOS activity (IC50 = 0.08 $\mu\textrm{g}$/$m\ell$) in the assay system determined by PGE2 and NO accumulation, respectively. The inhibitory potential of alantolactone on the PGE2 and NO production was well coincided with the suppression of COX-2 and iNOS protein and mRNA expression in LPS-induced macrophages. Furthermore, alantolactone inhibited NF-kB but not AP-l binding activity on nuclear extracts evoked by LPS-stimulated macrophage cells, suggesting the possible involvement of NF-kB in the regulation of COX-2 and iNOS expression. In further study with COX-2-expressing human colon HT-29 cells, alantolactone inhibited the cell proliferation, down-regulated COX-2, and inhibited the ERK phosphorylation in the early time. These results suggest that a natural sesquiterpenoid alantolactone might be a potential lead candidate for further developing COX-2 or iNOS inhibitor possessing cancer chemopreventive or anti-inflammatory activity

• Proceedings of the PSK Conference
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• 2002.10a
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• pp.320.2-320.2
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• 2002

Macrophages activated by lipopolysaccharide (LPS) are known to induce several proinflammatory proteins including COX-2. iNOS and TNF which produce chemical mediators involved in inflammatory response. Sophoricoside and its analogs (genistin, genistein and orobol) from Sophora japonica (Leguminosae) showed differential inhibitory effects on COX-1 and 2 activities. Sophoricoside and genistin shwoed IC50 values of 4 uM and 6 uM on COX-2 activity and of 1,497 uM and 135 uM on COX-1 activity, respectively. Genistein and orobol showed IC50 values of 3 uM on COX-2 activity and of 28 uM and 18 uM on COX-1 activity. respectively. Therefore. the legume isoflavonoids to be selective COX-2 inhibitors. However. sophoricoside and its analogs did not show inhibitory effects of COX-2, iNos and TNF transcripts. which were identified by the RT-PCR.

• 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.

• 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.

• Natural Product Sciences
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• v.3 no.1
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• pp.19-28
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• 1997

Constitutive cyclooxygenase (COX-I) is present in cells under physiological conditions, whereas inducible cyclooxygenase (COX-II) is induced by some cytokines, mitogens, and endotoxin presumably in pathological conditions such as inflammation. We have evaluated the inhibitory effects of solvent fractionated extracts of natural products on the activities of COX-I and COX-II. Oxygen uptake COX assay was performed, as a primary screening from the tissue extracts of bovine seminal vesicles (BSV), by monitoring the initial rate of oxygen uptake using an oxygen electrode. Additionally, we evaluated plant extracts for the inhibitory effects of COX-I (in HEL cells) and COX-II (in lipopolysaccharide activated J774A.1 macrophages) using thin layer chromatography of prostanoids produced from $^{14}C-labelled$ arachidonic acid (AA). The use of such models of COX-I and COX-II assay will lead to the identification of specific inhibitors of cyclooxygenases with presumably less side effects than present therapies. Inhibitory effects of 50 kinds of plant extracts on the COX-I and COX-II activities were determined and the active fractions were found in the ethyl acetate fractions of Dryopteris crassirhizoma (roots), Amomum cardamomum (roots), Triticum aestivum (seeds), Perilla sikokiana (leaves), Anemarrhena asphodeloides (roots). Especially, the ethyl acetate fraction of Dryopteris crassirhizoma (roots), which exhibited the strong inhibition against BSV COX $(IC_{50},\;65.4\;{\mu}g/ml)$, COX-I $(IC_{50},\;8.5\;{\mu}g/ml)$, and COX-II $(IC_{50},\;17.2\;{\mu}g/ml)$, is under investigation to isolate active principles using activity-guided fractionation method.