• 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.

• Reproductive and Developmental Biology
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• v.28 no.2
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• pp.89-94
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• 2004

This study was conducted to determine expression of acyl-CoA synthetase 4(ACS4), which is involved in converts arachidonic acid to postaglandins, in the mouse uterus during pregnancy. In arachidonic acid metabolism, acyl-CoA synthetase plays a key role in the esterification of free arachidonic acid into membrane phospholipids. Following its release by the action of calcium dependent phospholipases, free arachidonic acid is believed to be rapidly converted to arachidonoyl-CoA and reesterified into phospholipids in order to prevent excessive synthesis of prostaglandins. Here we demonstrate that ACS4 gene are differentially regulated in the peri-implatation mouse uterus. During the preimplantation period(days 0.5∼3.5), the ACS4 gene was expressed in the uterus until day 3.5 after which the expression was downregulated. The expression of cPLA2, COX1, and COX2 gene was similar to that of ACS4 gene in the preimplantation periods. However expression levels of COX1 gene show much variation on the various days of pregnancy examined. These data, suggest that ACS4 expression in preimplantation period is involved in initial attachment reaction with cPLA2, COX1, and COX2 gene.

• IMMUNE NETWORK
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• v.6 no.3
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• pp.123-127
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• 2006

Background: Caveolin-1 is a principal component of caveolae membranes in vivo. Although expression of caveolae structure and expression of caveolin family, caveolin-1, -2 and -3, was known in chondrocytes, the functional role of caveolae and caveolins in chondrocytes remains unknown. In this study, we investigated the role of caveolin-1 in articular chondrocytes. Methods: Rabbit articular chondrocytes were prepared from cartilage slices of 2-week-old New Zealand white rabbits by enzymatic digestion. Caveolin-1 cDNA was transfected to articular chondrocytes using LipofectaminePLUS. The cyclooxygenase-2 (COX-2) expression levels were determined by immunoblot analysis, immunostaining, immunohistochemistry, and prostaglandin $E_2\;(PGE_2)$ assay was used to measure the COX-2 activity. Results: Ectopic expression of caveolin-1 induced COX-2 expression and activity, as indicated by immunoblot analysis and $PGE_2$ assay. And also, overexpression of caveolin-1 stimulated activation of p38 kinase and ERK-1/-2. Inhibition of p38 kinase and ERK-1/-2 with SB203580 and PD98059, respectively, led to a dose-dependent decrease COX-2 expression and $PGE_2$ production in caveolin-1-transfected cells. Conclusion: Taken together, our data suggest that ectopic expression of caveolin-1 contributes to the expression and activity of COX-2 in articular chondrocytes through MAP kinase pathway.

• IMMUNE NETWORK
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• v.11 no.6
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• pp.364-367
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• 2011

Background: Prostaglandins (PGs) play pathogenic and protective roles in inflammatory diseases. The novel concept of PGs as immune modulators is being documented by several investigators. By establishing an in vitro experimental model containing human follicular dendritic cell-like cells, HK cells, we reported that HK cells produce prostaglandin $E_2$ ($PGE_2$) and prostaglandin $I_2$ ($PGI_2$) and that these PGs regulate biological functions of T and B cells. Methods: To investigate the respective contribution of cyclooxygenase-1 (COX-1) and COX-2 to $PGE_2$ and $PGI_2$ production in HK cells, we performed siRNA technology to knock down COX enzymes and examined the effect on PG production. Results: Both $PGE_2$ and $PGI_2$ productions were almost completely inhibited by the depletion of COX-2. In contrast, COX-1 knockdown did not significantly affect PG production induced by lipopolysaccharide (LPS). Conclusion: The current results suggest that mPGES-1 and PGIS are coupled with COX-2 but not with COX-1 in human follicular dendritic cell (FDC) and may help understand the potential effects of selective COX inhibitors on the humoral immunity.

• Parasites, Hosts and Diseases
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• v.53 no.5
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• pp.641-645
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• 2015

Fascioliasis, a food-borne trematode zoonosis, is a disease primarily in cattle and sheep and occasionally in humans. Water dropwort (Oenanthe javanica), an aquatic perennial herb, is a common second intermediate host of Fasciola, and the fresh stems and leaves are widely used as a seasoning in the Korean diet. However, no information regarding Fasciola species contamination in water dropwort is available. Here, we collected 500 samples of water dropwort in 3 areas in Korea during February and March 2015, and the water dropwort contamination of Fasciola species was monitored by DNA sequencing analysis of the Fasciola hepatica and Fasciola gigantica specific mitochondrial cytochrome c oxidase subunit 1 (cox1) and nuclear ribosomal internal transcribed spacer 2 (ITS-2). Among the 500 samples assessed, the presence of F. hepatica cox1 and 1TS-2 markers were detected in 2 samples, and F. hepatica contamination was confirmed by sequencing analysis. The nucleotide sequences of cox1 PCR products from the 2 F. hepatica-contaminated samples were 96.5% identical to the F. hepatica cox1 sequences in GenBank, whereas F. gigantica cox1 sequences were 46.8% similar with the sequence detected from the cox1 positive samples. However, F. gigantica cox1 and ITS-2 markers were not detected by PCR in the 500 samples of water dropwort. Collectively, in this survey of the water dropwort contamination with Fasciola species, very low prevalence of F. hepatica contamination was detected in the samples.

• YAKHAK HOEJI
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• v.51 no.5
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• pp.313-317
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• 2007

A series of luotonin A homologues and their aza-analogues were prepared and evaluated their inhibitory activities on COX-1 and 2 as well as their selectivities on COX-2. The aza-analogue of dimethylene-bridged homologue of luotonin A, 3,3'-dimethylene-2-(1',8'-naphthyrid-2'-yl)-4(3H)-quinazolinone (2b), exhibited strongest inhibitory activity against COX-1 and COX-2 dependent phase of prostaglandin $D_2$ generation in mouse bone marrow-derived mast cells in a concentration-dependent manner with an $IC_{50}$ of 39.3 and $1.89{\mu}M$, respectively. Selectivity of 2b on COX-2 over COX-1 was 21 which implied 2b can be a potential lead for the development of selective COX-2 inhibitor.

• Proceedings of the PSK Conference
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• 2002.10a
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• pp.292.1-292.1
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• 2002

In order to understand the mechanism of action of TCDD. we have examined the effect of COX-inhibitors on cypla1 activity. We observed the effect of COX-inhibitor on EROD activity in C57BL/6 mouse in vovo. And we also evaluated the effect of COX-inhibitors on cypla1 mRNA. mouse cyplal promoter activity and EROD activity in Hepa cell. When Aspirin were pretreated with 3MC in vivo, the EROD activity that was stimulated by 3MC was inhibited. (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 $NF-{\kappa}B$.

• ALGAE
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• v.27 no.2
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• pp.83-94
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• 2012

The taxonomic distinctiveness and cosmopolitan distributions of the red algae $Gelidium$ $crinale$ and $G.$ $pusillum$ remain unclear. Both species were first described in Devon in southwestern England; namely in Ilfracome for $G.$ $crinale$ and Sidmouth for $G.$ $pusillum$. We analyzed mitochondrial $cox$1 and plastid $rbc$L sequences from specimens collected in East Asia, Australia, Europe and North America. In all phylogenetic analyses of $cox$1 and $rbc$L sequences, $G.$ $crinale$ was distinct from congeners of the genus. The analyses also revealed a sister relationship with the $G.$ $coulteri$ and $G.$ $capense$ clade. Nineteen $cox$1 haplotypes were identified for $G.$ $crinale$, and they were likely geographically structured. Despite the distinctiveness in both $cox$1 and $rbc$L datasets, the sister relationship of $G.$ $pusillum$ in the genus was not resolved. Our $cox$1 and $rbc$L datasets indicate that $G.$ $crinale$ is a cosmopolitan species, found in East Asia, Australia, Europe and North America, while the distribution of $G.$ $pusillum$ is restricted to Europe and Atlantic North America. Our results suggest that infraspecific classification of $G.$ $pusillum$ may be abandoned.

• Archives of Pharmacal Research
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• v.29 no.12
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• pp.1102-1108
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• 2006

An in vitro bioassay-guide revealed that the methanol (MeOH) extract of the stem bark of Populus davidiana showed considerable inhibitory activity against cyclooxygenase (COX-1, COX-2). Continuous phytochemical study of the MeOH extract of this plant led to the isolation of ten flavonoids; sakuranetin (1), rhamnocitrin (2), 7-O-methylaromadendrin (3), naringenin (4), eriodictyol (5), aromadendrin (6), kaempferol (7), neosakuranin (8), sakuranin (9) and sakurenetin-5,4'-di-${\beta}$-D-glucopyranoside (10). Their structures were identified on the basis of their physicochemical and spectroscopic analyses. The isolated compounds, 1-10, were tested for their inhibitory activities against COX-1 and COX-2. Compound 7 was found to have potent inhibitory effect on COX-1 and a moderate effect on COX-2, meanwhile, compounds 1-6 showed moderate inhibition against COX-1 only. Moreover, compounds 5-8 exhibited suppressive effects on xanthine oxidase (XO). These results may explain, in part, the traditional uses of P. davidiana in ethnomedicine.