• Archives of Pharmacal Research
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• v.24 no.6
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• pp.552-556
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• 2001

Histamine and arachidonic acid (AA) release was measured using the P2-purinoceptor antaongists, phospholipase $A_2{\;}(PLA_2)$ and cyclooxygenase (COX)/lipoxygenase (LOX) inhibitors to determine whether or not ATP-induced histamine release is associated with arachidonic acid (AA) release in rat peritoneal mast cells. ATP increased histamine release in a dose dependent manner, whereas adenosine did not. PPADS (a selective P2X-purinoceptor antagonist) and suramin (a nonselective P2X,2Y-purinoceptor antagonist) inhibited ATP-induced histamine release in a dose dependent manner. However, RB-2 (a P2Y-purinoceptor antagonist) did not block ATP-induced histamine release. Manoalide and oleyloxyethyl phosphorylcholine (OPC), secretory PLA$_2$ inhibitors, also inhibited ATP-induced histamine release dose-dependently. Both COX inhibitors (ibuprofen and indomethacin) and LOX inhibitors (baicalein and caffeic acid) inhibited ATP-induced histamine in a dose dependent manner. ATP significantly increased [$^3H$]AA release by 54%. PPADS and suramin significantly inhibited ATP-induced [3H]Ph release by 81% and 39%, respectively. ATP-induced histamine release was significantly inhibited by a variety of protein kinase inhibitors, such as bisindolmaleimide, genistein, methyl 2,5-dihydroxycinnamate, W-7 and trifluoperazine. Overall, the results suggest that ATP-induced histamine release is in part related to the PLA2-mediated AA metabolism and P2X-purinoceptors.

• Proceedings of the PSK Conference
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• 2000.04a
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• pp.162.2-162.2
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• 2000

• Proceedings of the PSK Conference
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• 2003.10b
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• pp.65.2-65.2
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• 2003

88 selective COX-2 inhibitors belonging to three chemical classes (triaryl rings, diaryl cycloalkanopyrazoles, and diphenyl hydrazides) were studied using comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA). Partial least squares analysis produced statistically significant models with q values of 0.84 and 0.79 for CoMFA and CoMSIA, respectively. The key spatial properties were detected by careful analysis of the isocontour maps. The binding energies calculated from flexible docking correlated with inhibitory activities by the least-squares fit method. (omitted)

• Proceedings of the PSK Conference
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• 2000.10a
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• pp.213.3-214
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• 2000

• Proceedings of the PSK Conference
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• 2002.04a
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• pp.138.2-138.2
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• 2002

• Proceedings of the PSK Conference
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• 2003.10b
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• pp.113.2-113.2
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• 2003

Inducible cyclooxygenase-2 (COX-2) has been implicated in the processes of inflammation and carcinogenesis. Thus, the potential COX-2 inhibitors have been considered as anti-inflammatory or cancer chemopreventive agents. In this study, we investigated the effect of Caffeoyl-4-dihydrocaffeoyl quinic acid (CDCQ) isolated from Salicornia herbacea on the expression of cyclooxygenase (COX-2) in lipopolysaccharide (LPS)-activated RAW 264.7 macrophages. When CDCQ was treated with LPS, the prostaglandin $E_2$ production and COX-2 gene expression induced by LPS were markedly reduced in a dose-dependent manner. (omitted)

• Journal of Hospice and Palliative Care
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• v.8 no.1
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• pp.57-64
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• 2005

Cyclooxygenase-2 (COX-2) selective inhibitors were specifically developed to reduce the risks of gastrointestinal bleeding associated with other NSAID drugs. However, the APPROVe (Adenomatous Polyp Prevention on VIOXX) trials revealed that rofecoxib sometimes exerts prothrombotic effects. Meanwhile, cancer patients, who also carry a risk of thrombosis due to a variety of mechanisms, are often treated with COX-2 selective inhibitors, due to their relative gastrointestinal safety. This report concerns the case of a 46-year old woman with advanced cervical cancer, who had been treated with opioids and a COX-2 selective inhibitor (celecoxib) for 2 months, for the relief of pain associated with her cancer. The patient was admitted due to swelling of the left leg, which was also accompanied by pain. A computerized tomography scan revealed deep vein thrombosis occurring in multiple veins of both legs. After the administration of low-molecular weight heparin and oral warfarin, the patient's symptoms were relieved initially. However, her prothrombin time was found to be prolonged, necessitating the discontinuation of anticoagulation therapy. The patient's dyspnea worsened, ultimately resulting in her death. In conclusion, the administration of cox-2 selective inhibitors should be carefully considered in patients with a number of different risk factors, and assessed on a case-by-case basis.

• Proceedings of the PSK Conference
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• 2002.04a
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• pp.186.1-186.1
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• 2002

• Bulletin of the Korean Chemical Society
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• v.27 no.6
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• pp.933-935
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• 2006

• 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.