• 한국독성학회:학술대회논문집
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• 한국독성학회 2001년도 International Symposium on Signal transduction in Toxicology
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• pp.14-21
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• 2001

Many epidemiological studies have revealed that the use of aspirin or other non-steroidal anti-inflammatory drugs (NSAIDs) can reduce the risk of colon cancer. Since the well-documented pharmacological action of aspirin and other NSAIDs is the inhibition of cyclooxygenase [COX, the rate-limiting enzyme in prostaglandin (PG) biosynthesis], it has been inferred that the beneficial effect of NSAIDs may be mediated through the inhibition of PG biosynthesis.(omitted)

• 대한두경부종양학회:학술대회논문집
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• 대한두경부종양학회 2001년도 제17차 학술대회 및 제6차 심포지움
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• pp.72-72
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• 2001

• 대한약학회:학술대회논문집
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• 대한약학회 2001년도 Proceedings of International Convention of the Pharmaceutical Society of Korea
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• pp.208.3-209
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• 2001

• 대한약학회:학술대회논문집
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• 대한약학회 2000년도 NEW STRATEGY FOR DRUG DEVELOPMENT IN POST-GENOMIC ERA(대한약학회)
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• pp.232.1-232.1
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• 2000

• Biomolecules & Therapeutics
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• 제19권1호
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• pp.27-32
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• 2011

The activation of microglia induces the overproduction of inflammatory mediators that are responsible for the neurodegenerative disorders including Alzheimer's disease and Parkinson's disease. The large amounts of prostaglandin $E_2$ ($PGE_2$) produced by inducible cyclooxygenase (COX-2) is one of the main inflammatory mediators that can contribute to neurodegeneration. The inhibition of COX-2 thus may provide therapeutic strategy for the treatment of neurodegenerative diseases. From the activity-guided purification of EtOAc soluble fraction of Siegesbeckia glabrescens, four compounds were isolated as inhibitors of $PGE_2$ production in LPS-activated microglia. Their structures were determined as 3, 4'-dimethylquercetin (1), 3, 7-dimethylquercetin (2), 3-methylquercetin (3) and 3, 7, 4'-trimethylquercetin (4) by the mass and NMR spectral data analysis. The compounds 1-4 showed dose-dependent inhibition of $PGE_2$ production in LPS-activated microglia with their $IC_{50}$ values of 7.1, 4.9, 4.4, $12.4\;{\mu}M$ respectively. They reduced the expression of protein and mRNA of COX-2 through the inhibition of I-${\kappa}B{\alpha}$ degradation and NF-$\kappa}B$ activity that were correlated with the inactivation of p38 and ERK. Therefore the active compounds from Siegesbeckia glabrescens may have therapeutic effects on neuro-inflammatory diseases through the inhibition of overproduction of $PGE_2$ and suppression of COX-2 overexpression.

• 동의생리병리학회지
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• 제21권4호
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• pp.907-915
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• 2007

In this study the effect of water extract of Sophora tonkinensis Gapnep (RST) was investigated on the growth of human lung carcinoma A549 cells. Exposure of A549 cells to RST resulted in the growth inhibition in a dose-dependent manner as measured by MTT assay. The antiproliferative effect by RST treatment in A549 cells was associated with morphological changes such as membrane shrinking and cell rounding up. RST treatment did not induce the cell cycle arrest and the levels of tumor suppressor p53 as well as cyclin-dependent kinase inhibitor p21(WAF1/CIP1). It was found that RST treatment decreased the levels of cyclooxygenase (COX) -2 mRNA and protein expression without significant changes in the expression of COX-1 and inducible nitric oxide synthase (iNOS), which was correlated with a decrease in prostaglandin E2 (PGE2) synthesis. RST treatment also slightly inhibited the levels of human telomerase reverse transcriptase (hTERT) mRNA and protein expression, and the activity of telomerase. Taken together, these findings suggested that RST-induced inhibition of human lung carcinoma A549 cell growth was aoosciated with the inhibition of COX-2 expression and PGE2 production. These results provided important new insights into the possible molecular mechanisms of the anti-cancer activity of RST.

• Biomolecules & Therapeutics
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• 제8권1호
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• pp.73-77
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• 2000

Rheum undulatum L. has been used as Rhei Radix in Korean Pharmacopea although their pharmacological effects were not studied much. In this studym, we tested anti-inflammatory effect as a representative activity of Rheum undulatum L. extracts using cyclooxygenase (COX)-2 inhibition. Murine macrophage, Raw 264.7 cells were incubated with lipopolysaccharide (1 $\mu\textrm{g}$/ml) to induce COX-2. The prostagladin $E_2$ ($PGE_2$) levels as an indicator of COX-2 activity were determined in the culture medium using ELISA. Inhibition of acetylsalicylic acid (ASA) as a standard, aloe-emodin, chrysophanol, rhein, 80% ethanol extract of Rheum undulatum L. (Ex) and ether fraction (Fr) after acid hydrolysis of Rheum undulatum L. were tested in induced COX-2 described above. $IC_{50}$ values were 0.082 $\mu\textrm{g}$/ml for ASA. 181 $\mu\textrm{g}$/ml for aloe-emodin, 3.65 $\mu\textrm{g}$/ml for emodin, 144 $\mu\textrm{g}$/ml for chrysophanol, 39.8 $\mu\textrm{g}$/ml for rhein, 141 $\mu\textrm{g}$ of herb/ml for Ex, and 95.7 $\mu\textrm{g}$ of herb/ml for Fr. We found that Ex and Fr of Rheum undulatum L. were more effective than other anthraquinones, since their $IC_{50}$ are lower than others.

• 대한한의학회지
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• 제25권3호
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• pp.90-98
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• 2004

Objectives : The present study was undertaken to investigate the molecular mechanisms of Ichungwhan for inhibition of cyclooxygenase-2 (COX-2) gene expression via suppression of NF-κB (nuclear factor κB) using aged rats. NF-κB is the most important modulator of inflammation and NF-κB regulates the gene expression of several pro-inflammatory cytokines, such as COX-2. Methods : In the experiment, we investigated the scavenging property of Ichungwhan on reactive species (RS) including nitrogen-derived species (RNS), measured by DCF-DA (2,7-dichlorodihydrofluorexcein diacetate) / DHR 123 (dihydrorhodamine 123) assay. Protein expression levels of COX-2, NF-κB, p-ERK and p-p38 were assayed by western blot. Results : We showed that Ichungwhan inhibits RS including RNS and inhibits NF-κB activation by blocking the dissociation of inhibitory IκB-β via suppression of IKK pathway. Also, Ichungwhan inhibits COX-2 gene expression. Conclusions : These findings suggest that Ichungwhan modulates COX-2 gene expression via suppression of the NF-κB pathway.

• Journal of Ginseng Research
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• 제38권1호
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• pp.34-39
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• 2014

Cigarette smoke is considered a major risk factor for vascular diseases. There are many toxic compounds in cigarette smoke, including acrolein and other ${\alpha},{\beta}$-unsaturated aldehydes, which are regarded as mediators of inflammation and vascular dysfunction. Furthermore, recent studies have revealed that acrolein, an ${\alpha},{\beta}$-unsaturated aldehyde in cigarette smoke, induces inflammatory mediator expression, which is known to be related to vascular diseases. In this study, we investigated whether Korean Red Ginseng (KRG) water extract suppressed acrolein-induced cyclooxygenase (COX)-2 expression in human umbilical vein endothelial cells (HUVECs). Acrolein-induced COX-2 expression was accompanied by increased levels of phosphorylated p38 in HUVECs and KRG inhibited COX-2 expression in HUVECs. These results suggest that KRG suppresses acrolein-induced COX-2 expression via inhibition of the p38 mitogen-activated protein kinase signaling pathway. In addition, KRG exhibited an inhibitory effect on acrolein-induced apoptosis, as demonstrated by annexin Vepropidium iodide staining and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling assay. Consistent with these results, KRG may exert a vasculoprotective effect through inhibition of COX-2 expression in acrolein-stimulated human endothelial cells.

• Archives of Pharmacal Research
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• 제26권10호
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• pp.832-839
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• 2003

Activated macrophages express inducible isoforms of nitric oxide synthase (iNOS) and cyclooxygenase (COX-2), and produce excessive amounts of nitric oxide (NO) and prostaglandin E$_2$ (PGE$_2$), which play key roles in the processes of inflammation and carcinogenesis. The root of Paeonia lactiflora Pall., and the root cortex of Paeonia suffruticosa Andr., are important Chinese crude drugs used in many traditional prescriptions. 1,2,3,4,6-penta-O-galloyl-$\beta$-D-glucose (PGG) is a major bioactive constituent of both crude drugs. PGG has been shown to possess potent anti-oxidant, anti-mutagenic, anti-proliferative and anti-invasive effects. In this study, we examined the inhibitory effects of 1,2,3,4,6-penta-O-galloyl-$\beta$-D-glucose (PGG) isolated from the root of Paeonia lactiflora Pall. on the COX-2 and iNOS activity in LPS-activated Raw 264.7 cells, COX-1 in HEL cells. To investigate the structure-activity relationships of gallate and gallic acid for the inhibition of iNOS and COX-2 activity, we also examined (-)-epigallocatechin gallate (EGCG), gallic acid, and gallacetophenone. The results of the present study indicated that PGG, EGCG, and gallacetophenone treatment except gallic acid significantly inhibited LPS-induced NO production in LPS-activated macrophages. All of the four compounds significantly inhibited COX-2 activity in LPS-activated macrophages. Among the four compounds examined, PGG revealed the most potent in both iNOS ($IC_{50}$ = 18 $\mu\textrm{g}/mL$) and COX-2 inhibitory activity (PGE$_2$: $IC_{50}$ = 8 $\mu\textrm{g}/mL$ and PGD$_2$: $IC_{50}$ = 12 $\mu\textrm{g}/mL$), respectively. Although further studies are needed to elucidate the molecular mechanisms and structure-activity relationship by which PGG exerts its inhibitory actions, our results suggest that PGG might be a candidate for developing anti-inflammatory and cancer chemopreventive agents.