• Proceedings of the PSK Conference
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• 2003.04a
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• pp.248.3-249
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• 2003

A series of tetrahydroaminoacridine and their analogues were synthesized. Tetrahydroaminoacridine(tacrine) is an anticholinesterase agent used in the treatment of Alzheimer's disease. Introduction of piperidine group at the para position enhanced anti-inflamatory activity for Alzheimer's disease. We investigated their ability to inhibit cyclooxygenase-1 and 2 isoforms. (omitted)

• Natural Product Sciences
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• v.10 no.1
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• pp.1-10
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• 2004

Plant flavonoids possess anti-inflammatory activity in vitro and in vivo. Although the action mechanisms are not fully understood, recent studies have clearly shown that certain flavonoids, especially flavone derivatives, express their anti-inflammatory activity at least in part by modulation of proinflammatory gene expression such as cyclooxygenase-2, inducible nitric oxide synthase and various cytokines. This review summarizes the recent findings of flavonoids modulating expression of proinflammatory molecules.

• 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.

• Journal of Applied Biological Chemistry
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• v.64 no.4
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• pp.375-382
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• 2021

Biorenovation is a microbial enzyme-based structural modification of component compounds in natural products and synthetic compounds including plant extracts with the potential benefits of improved biological activities compared with its reaction substrates. In this study, we investigated the anti-inflammatory activity of Distylium racemosum leaf extract and D. racemosum leaf biorenovation extract (DLB). As a result, DLB inhibited nitric oxide, prostaglandin E2, and inflammatory cytokines including tumor necrosis factor-α, interleukin-6, interleukin-1β at non-toxic concentrations. In addition, DLB significantly inhibited inducible nitric oxide synthase and cyclooxygenase-2 on LPS-treated RAW 264.7 macrophages. Based on these results, we suggest that the DLB could be used as a potent anti-inflammatory agents. It also suggests that the application of biological evolution has potential usefulness to increase the practical value of natural products.

• 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.

• Korean Journal of Food Science and Technology
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• v.43 no.1
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• pp.110-113
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• 2011

Egg allergies are the most prevalent food hypersensitivity in children. The major egg allergens are proteins, such as ovalbumin (OVA) and ovomucoid (OVM), which are mainly contained in egg whites. OVA is the major protein in egg white, comprising 54% of the total protein content. OVA has been widely used in experimental inhalant and dietary allergy animal models, but its mechanism has not been clearly identified. In this study, we showed that OVA induced nuclear factor-${\kappa}B$ activation. OVA also induced the expression of cyclooxygenase-2 and inducible nitric oxide synthase. These data suggest new approaches for developing efficient anti-allergic strategies.

• Biomedical Science Letters
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• v.15 no.2
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• pp.141-146
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• 2009

Paclitaxel, an antimicrotubule agent, binds to beta-tubulin in the microtubule and stabilizes the polymer, thereby repressing dynamic instability. Here, we have demonstrated that microtubule cytoskeletal architecture involved in regulation of the COX-2 expression in chondrocyte treated with paclitaxel. Paclitaxel enhanced COX-2 expression and prostaglandin E2 production, as indicated by the Western blot analysis, reverse transcriptase PCR(RT-PCR) and immunofluorescence staining, and $PGE_2$ assay, respectively. In our previous data have shown that paclitaxel treatment stimulated activation of ERK-1/2 and p38 kinase(Im et al., 2009). SB203580, an inhibitor of p38 kinase, blocked the induction of COX-2 expression by paclitaxel. Also PD98059, an inhibitor of ERK-1/2 kinase was blocked the induced COX-2 expression. These results indicate that activation of ERK-1/2 and p38 kinase is required for COX-2 expression induced by paclitaxel in rabbit articular chondrocytes.

• Journal of Acupuncture Research
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• v.23 no.2
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• pp.61-72
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• 2006

Objectives : Human chondrocytes co-treated with Buthus martensi Karsch herbal acupuncture solution(BMK-HAS) extract produced significantly less NO compared with chondrocytes stimulated with $IL-1{\beta}$ alone Methods : Activation and translocation of and NF-kB DNA binding activity were determined by Western blotting and specific enzyme-linked immunosorbent assay. Results : The inhibition of NO production correlated with the suppression of induction and expression of nuclear factor-kB (NF-kB) and activation protein-1 (AP-1)-dependent gene. BMK-HAS inhibited the activation and translocation of NF-kB to the nucleus, indicating that BMK-HAS inhibits the $IL-1{\beta}-induced$ production of NO in human chondrocytes by interfering with the activation of NF-kB through a novel mechanism. In addition, BMK-HAS reduced prostaglandin E2 (PGE2)production in mouse peritoneal macrophages stimulated with lipopolysaccharide, whereas no influence on the activity of inducible NO synthase (iNOS), cyclooxygenase-2 (COX-2) or cyclooxygenase-1 (COX-1) was observed. My data, therefore, suggest that BMK-HAS may be a therapeutically effective inhibitor of $IL-1{\beta}-induced$ inflammatory effects that are dependent on NF-kB activation in human OA chondrocytes. Conclusion : The results indicate that BMK-HAS exerts anti-inflammatory effects related to the inhibition of neutrophil functions and of NO and PGE2 production, which could be due to a decreased expression of iNOS and COX-2 through the transcription factors NF-kB and AP-1.

• The Journal of the Korean Society for Microbiology
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• v.34 no.5
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• pp.479-489
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• 1999

Invasion of enteric bacteria, such as Salmonella and invasive E. coli, into intestinal epithelial cells induces proinflammatory gene responses and finally epithelial cell apoptosis. In this study, we asked whether invasive bacterial infection of human intestinal epithelial cells could upregulate cyclooxygenase-2 (COX-2) gene expression and whether increased COX-2 expression could influence intestinal epithelial cell apoptosis. Expression of COX-2 mRNA and prostaglandin (PG) $E_2$ production were upregulated in HT-29 colon epithelial cells which were infected with S. dublin or invasive E. coli, as examined by quantitative RT-PCR and radioimmunoassay. Inhibition of COX-2 expression and $PGE_2$ production using NS-398, a specific COX-2 inhibitor, showed a significant increase of epithelial cell apoptosis and caspase-3 activation in HT-29 cells infected with invasive bacteria. However, the addition of valerylsalicylate, a specific COX-1 inhibitor, did not change apoptosis in S. dublin-infected HT-29 cells. These results suggest that up regulated COX-2 expression and $PGE_2$ production in response to invasive bacterial infection could contribute to host defense by inhibiting apoptosis of intestinal epithelial cells.

• Journal of the Korean Society of Food Science and Nutrition
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• v.27 no.1
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• pp.175-181
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• 1998

The relation between lipid peroxidation and thrombotic reaction were investigated in streptozotocin (STZ)-induced diabetic rats. Sprague-Dawley male rats weighing 100$\pm$10gm were randomly assigned to normal and STZ-induced diabetic group(DM). Diabetes was experimentally induced by intravenous injection of 55mg/kg of body weight of STZ in citrate buffer(pH 4.3) after 4 weeks feeding of basal diet. Animals were sacrificed at the 6th day of diabetic states. Body weight gains were lower in diabetic group after STZ injection. Serum levels of thiobarbituric acid reacting substances(TBARS) that were markedly increased in DM group compared with of normal group. TBARS levels of HDL and LDL were similar patterns to total TBARA of serum. Activities of platelet phospholipase A2(PLA2) were higher in diabetic group than those of normal group. Activities of platelet cyclooxygenase were 106% in DM group than normal group. Platelet thromboxane A2(TXA2) formation was increased in DM group than normal group. Production of aortic prostacyclin(PGI2) was lower in diabetic group than that of normal group. PGI2/TXA2 ratios were decreased by 55% in DM groups than those of normal group. The present results indicate that STZ-induced diabetic rats are more sensitive to oxidative stess which leads to acceleration of lipid peroxidation and platelet aggregability. In conclusion, accelerating effect of lipid peroxidation and thrombogenesis in diabetic state is regareded to be resulted from enhancement of PLA2 activity and arachidonic acid metabolism, inhibition of antiaggrgating agent and aortic PGI2 formation.