• Proceedings of the PSK Conference
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• 2002.10a
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• pp.278.1-278.1
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• 2002

In the previous study, we reported that NQ12, a vitamin K antagonist. showed a potent antithrombotic and antiplatelet activities. In order to elucidate the antiplatelet activity of NQ12. we investigated the effect of NQ12 on arachidonic acid cascade parameters such as cPLA2. cyclooxygenase (COX), and the downstream production such as TxA2, PGD2 and 12-HETE. N012 inhibited COX activity in a concentration-dependent manner in U937 cells. (omitted)

• International Journal of Oral Biology
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• v.31 no.1
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• pp.21-26
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• 2006

Periodontopathogens including Porphyromonas gingivalis interact with host periodontal cells and the excessive subsequent host responses contribute a major part to the development of periodontal diseases. Cyclooxygenase(COX)-2-synthesized $PGE_2$ has detrimental activities in terms of periodontal pathogenesis. The present study investigated induction of COX-2 expression by P. gingivalis in human monocytic THP-1 cells. Live P. gingivalis increased expression of COX-2, but not that of COX-1, which was demonstrated at both mRNA and protein levels. Elevated levels of $PGE_2$ were released from P. gingivalis-infected THP-1 cells. Pharma-cological inhibition of p38 mitogen-activated protein kinase(MAPK) and extracellular signal-regulated kinase(ERK) substantially attenuated P. gingivalis-induced COX-2 mRNA expression. Indeed, activation of p38 MAPK and ERK was observed in P. gingivalis-infected THP-1 cells. Also, P. gingivalis induced activation of nuclear $factor-{\kappa}B\;(NF-{\kappa}B)$ which is an important transcription factor for COX-2. These results suggest that COX-2 expression is up regulated in P. gingivalis-infected monocytic cells, at least in part, via p38 MAPK, ERK, and $NF-{\kappa}B$.

• Environmental Mutagens and Carcinogens
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• v.25 no.4
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• pp.143-149
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• 2005

The identification of COX-2 (cyclooxygenase-2) has led to potential novel insights on disease pathogenesis (atherosclerosis, cancer, Alzheimer's disease) and the regulation of normal organ function. The present in vivo study with estrogen or soy-isoflavones has provided evidence for the association between COX-2 and ICAM-1 (Intercellular adhersion molecule-1). In the system of mature female rats, soy-isoflavones exerted more pronounced effect on ICAM-1 inhibitory and COX-2 stimulatory effect than estrogen. In the system of ovariectomized estrogen deficient rats, the down-regulatory properties of soy-isoflavones on ICAM-1 was less evident, whereas estrogen exerted the inhibitory activity. These results demonstrate that COX-2 limits adhersion molecule expression on rat aorta cells and suggest that COX-2 may play a protective role in cardiovascular system in mature female rats. Soy-isoflavones appear to have beneficial effect on vascular systems through modulation of ICAM-1 and COX-2, and these molecules appeared to be closely associated.

• The Journal of Korean Medicine
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• v.29 no.5
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• pp.111-117
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• 2008

Objectives and methods : Previous mechanistic studies suggest the cyclooxygenase-2 (COX-2) inhibitors represent the good candidates against tumor progression. MeOH extract of the stem barks of Euonymus alatus induced the strong inhibition of COX-2. A phenolic compound responsible for the anti- COX-2 known to involve in tumor adhesion and invasion has been studied through the methanol extracts. The compound, rosmarinic acid (ROS-A) was an ester of caffeic acid and 3,4-dihydroxyphenyllactic acid. ROS-A showed a strong inhibitory effect of COX-2 activity in a concentration-dependent manner. Then we have measured the IL-1${\beta}$, IL-6 and TNF-${\alpha}$ production related the immune regulation, induction of inflammatory related genes. Results and Conclusions :Hep3B cells produce proinflammatory cytokines of IL-1${\beta}$, IL-6 and TNF-${\alpha}$ while ROS A inhibited the cytokines production. Since IL-1${\beta}$, IL-6 and TNF-${\alpha}$ need the transcription factors such as nuclear factor- ${\kappa}$B (NF-${\kappa}$B) and activated protein-1 (AP-1), we measured the transcription factors. ROS-A inhibited the activation of p65, p50, c-Rel subunits of NF-${\kappa}$B and AP-1 transcription factors. These findings indicate that ROS A from the stem bark of E. alatus inhibits proliferation in metastatic cancer cells. It was suggested that stem barks of E. alatus could be suitable for anti-cancer drugs.

• Natural Product Sciences
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• v.2 no.1
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• pp.56-74
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• 1996

Prostaglandin $H_2$ synthase is the pharmacological target site of nonsteroidal antiinflammatory drugs. Inhibitory effects on cyclooxygenase activity of the synthase by extracts prepared from herbal medicines and wild plants in Korea have been estimated. Sixteen species out of 612 species exhibited more than 50% of inhibition on the enzyme activity. The active extracts prepared from Carex humilis, Celastrus orbiculatus, Eugenia caryophyllata, Gleditsia japonica var. koraiensis, Glycyrrhiza grabra, Glycyrrhiza uralensis, Gyrophora exculenta, Lespedeza maximowiczii, Morus alba, Persicaria conspicua, Prunus salicina, pterocarya stenoptera, Rheum undulatum, Vitis amurensis, and Vitis coignetiae have been sequentially washed with methylene chloride, ethyl acetate, n-butanol. Among the solvent fractions of the active herbal extracts, ethyl acetate fraction of Carex humilis exhibited the highest inhibitory effect on the cyclooxygenase activity of prostaglandin $H_2$ synthase.

• The Korean Journal of Physiology and Pharmacology
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• v.10 no.1
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• pp.45-50
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• 2006

Melittin-induced pain model has been known to be very useful for the study of pain mechanism. Melittin-induced nociceptive responses are reported to be modulated by the changes in the activity of excitatory amino acid receptor, calcium channel, spinal serotonin receptor and extracellular signaling-regulated kinase. The present study was undertaken to investigate the role of cyclooxygenase (COX) in the melittin-induced nociception. Changes in mechanical threshold, flinchings and paw thickness were measured before and after intraplantar injection of melittin in the rat hind paw. Also studied were the effects of intraperitonealy administered diclofenac (25 mg & 50 mg/kg), piroxicam (10 mg & 20 mg/kg) and meloxicam (10 mg & 20 mg/kg) on the melittin-induced nociceptions. Intraplantar injection of melittin caused marked reduction of mechanical threshold that was dose-dependently attenuated by non-selective COX inhibitor (diclofenac) and selective COX-1 inhibitor (piroxicam), but not by COX-2 inhibitor (meloxicam). Melittin-induced flinchings were strongly suppressed by non-selective COX and COX-1 inhibitor, but not by COX-2 inhibitor. None of the COX inhibitors had inhibitory effects on melittin-induced increase of paw thickness (edema). These experimental findings suggest that COX-1 plays an important role in the melittin-induced nociceptive responses.

• Archives of Pharmacal Research
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• v.27 no.4
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• pp.442-448
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• 2004

Wogonin (5,7-dihydroxy-8-methoxyflavone) is a down-regulator of cyclooxygenase-2 and inducible nitric oxide synthase expression, contributing to anti-inflammatory activity in vivo. For further characterization of modulatory activity on ploinflammatory gene expression in vivo, the effect of wogonin was examined in this experiment using animal models of skin inflammation. By topical application, wogonin inhibited an edematic response as well as ploinflammatory gene expression against contact dermatitis In mice. Wogonin inhibited ear edema ($19.4-22.6\%$) at doses of $50-200\;{\mu}g$/ear and down-regulated interleukin-$1{\beta}$ induction ($23.1\%$) at $200{\mu}g$/ear in phenol-induced simple irritation. Wogonin ($2{\times}50-2{\times}200{\mu}g$/ear) also inhibited edematic response ($51.2-43.9\%$) and down-regulated ploinflammatory gene expression of cyclooxygenase-2, interleukin-$1{\beta}$, interferon-$\gamma$, intercellular adhesion molecule-1 and inducible nitric oxide synthase with some different sensitivity against picryl chloride-induced delayed hypersensitivity reaction. All these results clearly demonstrate that wogonin is a down-regulator of ploinflammatory gene expression in animal models of skin inflammation. Therefore, wogonin may have potential for a new anti-inflammatory agent against skin inflammation.

• Proceedings of the Korean Society of Applied Pharmacology
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• 2003.11a
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• pp.96-96
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• 2003

Previously, wogonin (5,7-dihydroxy-8-methoxyflavone) was found to suppress proinflammatory enzyme expression including cyclooxygenase-2 (COX-2), contributing to in vivo anti-inflammatory activity against skin inflammation. However, the detailed effect on each skin cell type has not been understood. Therefore, present investigation was carried out to find the effect of wogonin on inflammation-associated gene expression from skin fibroblasts in culture using reverse transcriptase-polymerase chain reaction. As a result, it was found that wogonin (10 - 100 ${\mu}$M) clearly down-regulated COX -2 expression from NIH/3T3 cells treated with 12-O-tetradecanoylphorbol 13-acetate, interleukin-1${\beta}$ or tumor necrosis factor-a. But, the expression levels of COX-1, interleukin-1${\beta}$ and fibronectin were not significantly affected. This finding was well correlated with significant reduction of prostaglandin E$_2$(PGE$_2$) production by wogonin. As a comparison, NS-398 (selective cyclooxygenase-2 inhibitor) did not suppress COX -2 expression and other gene levels, while PGE$_2$production was potently reduced at 0.1 - 10 ${\mu}$M. All these results suggest that COX -2 down-regulation of skin fibroblasts may be, at least in part, one of anti-inflammatory mechanisms of wogonin against skin inflammation.

• Journal of Nutrition and Health
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• v.37 no.9
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• pp.763-770
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• 2004

This study was designed to compare the anti-carcinogenic effect of conjugated linoleic acid isomers on tumor incidence, cell proliferation and the levels of thromboxane (TX) B$_2$, prostaglandin (PG) E$_2$ and 1,2-diacylglycerol (DAG), and the related enzyme expression of cyclooxygenase (COX)-2 and protein kinase C (PKC) in colonic mucosa of 1,2-dimethy- lhydrazine (DMH) -treated rats. One hundred eight male Sprague Dawley rats were randomly divided into 3 groups depending on the types of CLA isomers, i.e. control group (no CLA contained), c9t11 group (cis-9, trans-11 CLA contained), and t10c12 group (trans-10, cis-12 CLA contained). The experimental diet was composed of protein at 20%, carbohydrate at 56.2%, and fat at 14.5% including 1.0% CLA isomers by weight. The experimental diet was fed for 30 weeks with the initiation of intramuscular injection of DMH, which was injected twice a week for 6 weeks to give total dose of 180 mg per kg body weight. Two CLA isomers (c9, t11, t10, c12) significantly reduced tumor incidence and cell proliferation by reducing the protein expression of COX-2 and PKC, and the level of TXB$_2$, PGE$_2$, and DAG in colonic mucosa. However, there was no significant difference in anti-carcinogenic effect between c9t11-CLA and t10c12-CLA.

• Archives of Pharmacal Research
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• v.25 no.3
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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.