• Journal of Korean Neurosurgical Society
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• 제38권4호
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• pp.287-292
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• 2005

Objective : Kainic acid[KA] enhances the expression of nitric oxide synthase, increases nitric oxide[NO], and thus evokes epileptic convulsion, which results in neuronal damage in the rat brain. NO may stimulate cyclooxygenase type-2 [COX-2] activity, thus producing seizure and neuronal injury, but it has also been reported that KA-induced seizure and neurodegeneration are aggravated on decreasing the COX-2 level. This study was undertaken to investigate whether the suppression of NO using the NOS inhibitor, N-nitro-L-arginine methyl ester[L-NAME], suppresses or enhances the activity of COX-2. Methods : Silver impregnation and COX-2 immunohistochemical staining were used to localize related pathophysiological processes in the rat forebrain following KA-induced epileptic convulsion and L-NAME pretreatment. Post-injection survival of the rat was 1, 2, 3days and 2months, respectively. Results : After the systemic administration of KA in rats, neurodegeneration increased with time in the cornu ammonis [CA] 3, CA 1 and amygdala, as confirmed by silver impregnation. On pretreating L-NAME, KA-induced neuronal degeneration decreased. COX-2 enzyme activities increased after KA injection in the dentate gyrus, CA 3, CA 1, amygdala and pyriform cortex, as determined by COX-2 staining. L-NAME pretreatment prior to KA-injection, caused COX-2 activities to increase compared with KA- injection only group by 1day and 2days survival time point. Conclusion : These results suggest that L-NAME has a neuroprotective effect on KA-induced neuronal damage, especially during the early stage of neurodegeneration.

• Archives of Pharmacal Research
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• 제26권5호
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• pp.383-388
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• 2003

Bee venom is used as a traditional medicine for treatment of arthritis. The anti-inflammatory activity of the n-hexane, ethyl acetate, and aqueous partitions from bee venom (Apis mellifera) was studied using cyclooxygenase (COX) activity and pro-inflammatory cytokines (TNF-$\alpha and IL-1\beta$) production, in vitro. COX-2 is involved in the production of prostaglandins that mediate pain and support the inflammatory process. The aqueous partition of bee venom showed strong dose-dependent inhibitory effects on COX-2 activity ($IC_{50} = 13.1 \mu$ g/mL), but did not inhibit COX-1 activity. The aqueous partition was subfractionated into three parts by molecular weight differences, namely, B-F1 (above 20 KDa), B-F2 (between 10 KDa and 20 KDa) and BF-3 (below 10 KDa). B-F2 and B-F3 strongly inhibited COX-2 activity and COX-2 mRNA expression in a dose-dependent manner, without revealing cytotoxic effects. TNF-$\alpha and IL-1\beta$ are potent pro-inflammatory cytokines and are early indicators of the inflammatory process. We also investigated the effects of three subfractions on TNF-$\alpha and IL-1\beta$ production using ELISA method. All three subfractions, B-F1, B-F2 and B-F3, inhibited TNF-$\alpha and IL-1\beta$production. These results suggest the pharmacological activities of bee venom on anti-inflammatory process include the inhibition of COX-2 expression and the blocking of pro-inflammatory cytokines (TNF-$\alpha and IL-1\beta$) production.

• Preventive Nutrition and Food Science
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• 제11권1호
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• pp.1-5
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• 2006

Conjugated linoleic acid (CLA) is a group of positional and geometric isomers of linoleic acid that have been used to reduce the incidence, growth and metastasis of breast, colon, prostate and gastric cancer in animals. CLA could reduce tumor growth by altering angiogenesis; a process requiring associated angiogenic factors such as vascular endothelial growth factor (VEGF). In this study, we determined whether CLA could modulate the expression of VEGF in murine mammary tumor cells and adipocytes. The c9, t11-CLA isomer reduced VEGF transcripts and protein when mammary tumor cells were stimulated with PMA. That isomer also reduced VEGF expression in un stimulated mouse 3T3-L1 adipocytes. Since VEGF can be regulated by cyclooxygenase-2 (COX-2), we determined whether CLA could alter COX-2 enzyme expression and $PGE_2$ production. The c9, t11-CLA isomer reduced not only COX-2 enzyme expression but also $PGE_2$ production. Thus, c9, t11-CLA could modulate neovascularization by alteration of VEGF expression from mammary tumor cells and adipocytes by reducing COX-2 metabolites.

• 한국독성학회:학술대회논문집
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• 한국독성학회 2003년도 춘계학술대회 논문집
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• pp.95.1-95
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• 2003

Ginger (Zingiber officinale Roscoe, Zingiberaceae) has a wide array of pharmacologic effects. Our previous studies have demonstrated that [6]-gingerol, a major pungent ingredient of ginger, inhibits mouse skin tumor promotion and anchorage-independent growth of cultured mouse epidermal cells stimulated with epidermal growth factor. In this study, we have investigated the molecular mechanisms underlying chemopreventive effects of [6]-gingerol on mouse skin carcinogenesis. Cyclooxygenase-2 (COX-2), a key enzyme in the formation of prostaglandins, has been recognized as a molecular target of many chemopreventive as well as anti-inflammatory agents. The murine COX-2 promoter contains several transcriptional elements, particularly those involved in regulating inflammatory processes. One of the essential transcription factors responsible for COX-2 induction is NF-kappa B. Topical application of [6]-gingerol inhibited the COX-2 expression through suppression of NF-kappa B activation in phorbol ester-treated mouse skin. [6]-Gingerol, through down-regulation of p38 MAPK, abrogated the DNA binding activity of NF-kappa B by blocking phosphorylation of p65/RelA at the Ser 536 residue. These findings suggest that [6]-gingerol exerts an anti-tumor promotional activity through inhibition of the p38 MAPK-NF-kappa B siganling cascade in mouse skin.

• 생명과학회지
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• 제21권10호
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• pp.1494-1499
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• 2011

${\beta}$-lapachone은 남미에 자생하는 lapacho 나무(Tabeuia avellanedae)의 수액에 함유된 quinone계열의 일종으로 많은 인체암세포에서 apoptosis를 유발하는 것으로 알려져 있다. 본 연구는 A549 인체폐암세포를 대상으로 ${\beta}$-lapachone에 의한 apoptosis 유발 과정에서 나타나는 또 다른 현상들을 조사하기 위하여 실시되었다. ${\beta}$-lapachone이 처리된 A549 세포는 처리 농도의 증가에 따라 생존율이 감소되었으며, 이는 apoptosis 유발과 연관이 있음을 MTT assay와 flow cytometry 분석을 통하여 확인하였다. ${\beta}$-lapachone에 의한 A549 세포의 증식억제는 종양억제유전자 p53과 cyclin-dependent kinase 저해제인 p21의 발현을 전사 및 번역 수준에서 증가시켰으며, p53 단백질의 인산화 증가와 연관성이 있었다. 또한 ${\beta}$-lapachone은 caspase-3과 -9를 활성화시켰으며, 활성화된 caspase-3의 기질 단백질들[poly(ADP-ribose) polymerase, ${\beta}$-catenin 및 phospholipase C-$\gamma$1]의 단편화를 유도하였다. 아울러 ${\beta}$-lapachone은 cyclooxygenase (COX)-2의 mRNA 및 단백질의 발현을 억제하였으나 COX-1의 발현에는 영향을 미치지 않았으며, ${\beta}$-lapachone에 의한 COX-2의 발현억제는 prostaglandin E2의 생성 저하에 관련이 있었다. 본 연구의 결과는 ${\beta}$-lapachone의 항암활성 기전의 이해와 더불어 ${\beta}$-lapachone이 폐암세포에서 강력한 항암활성이 있음을 보여 주는 것이다.

• 약학회지
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• 제42권6호
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• pp.558-566
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• 1998

Two isoforms of cyclooxygenase (COX) have been identified - COX-1, which is constitlitively expressed in most tissues, and the inducible form, COX-2, of which expression is induced by inflammatory signals and mitogens. It has been considered that the beneficial effects of NSAIDs are due to the inhibition of COX-2 activity and the side effects are from the inhibition of COX-1 activity. Therefore, it is essential to develop selective COX-2 inhibitor for developing new GI-tolerable NSAIDS. To discover new leads for developing selective COX-2 inhibitors, three-hundred extracts of natural products were primarily screened with the system of prostaglandin accumulation in LPS-stimulated mouse peritoneal macrophages. To identify whether these inhibitory activities of crude extracts on the accumulation of Prostaglandins were derived from direct action against COX-2, the effects of selected extracts on exogenous arachidonic acid-derived production of prostaglandins by LPS-stimulated macrophages were determined. Among them, 5 methanol extracts of natural products, such as Zingiberis Rhizoma, Alpinae Officinarum Rhizoma, Caryophilli Flos, Scutellariae Radix, Dalbergia ordorifera. inhibited more than 70% of the prostaglandin production in LPS-stimulated mouse peritoneal macrophages at a con-centration of 1${\mu}$g/ml.

• Journal of Acupuncture Research
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• 제23권2호
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• pp.91-102
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• 2006

Objectives : Ulmus davidiana Planch (UD) has long been known to have anti-inflammatory and protective effects on damaged tissue, inflammation and bone among other functions. Methods : This study was undertaken to address whether the water extract of the bark of UD could modulate proliferation of mouse osteoclasts in vitro and to investigate its effect on cyclooxygenase-2 (COX-2), which converts arachidonic acid to prostaglandin E2 (PGE2) and is highly expressed in osteoclasts. Mouse osteoclasts were tested in vitro for growth inhibition, proliferation cell nuclear antigen expression, and COX-2 activity and expression after treatment with UD extract. Results : Its effects were compared with those of indomethacin (a nonselective COX inhibitor) and celecoxib (a selective COX-2 inhibitor) by Cell viability assay, Cell cycle analysis, Immunohistochemical analysis of PCNA expression, Western blot analysis and PGE2 Enzyme immunoassay (EIA). UD demonstrated a strong growth inhibitory action in both tested osteoclasts cells. The IC50s were $10\;{\mu}g/ml$ for UD, $6\;{\mu}M$ for celecoxib and $42\;{\mu}M$ for indomethacin. UD, as well as celecoxib and indomethacin, suppressed proliferation cell nuclear antigen expression and PGE2 synthesis in osteoclasts. UD inhibited COX-2 expression, whereas celecoxib inhibited COX-2 activity directly. Conclusion : UD selectively and effectively inhibits osteoclasts cell growth in vitro. Inhibitory action of PGE2 synthesis via suppression of COX-2 expression may be responsible for its anti-inflammatory activity.

• 한국독성학회:학술대회논문집
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• 한국독성학회 2002년도 Molecular and Cellular Response to Toxic Substances
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• pp.135-135
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• 2002

Cyclooxygenase-2 (COX-2) is an inducible enzyme expressed in response to a variety of cytokines and other proinflammatory stimuli. It has been known that aberrant up-regulation of COX-2 is associated with resistance to apoptosis.(omitted)

• Journal of Acupuncture Research
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• 제23권2호
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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.

• 동의생리병리학회지
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• 제18권1호
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• pp.254-259
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• 2004

Jeongshin-tang (JST) is a Korean herbal prescription, which has been successfully applied for the various neuronal diseases. However, it's effect remains unknown in experimental models. To investigate the biological effect of JST in Alzheimer's disease (AD) in vitro model, we analized the production of interleukin (IL)-6 and IL-8, and expression of cyclooxygenase (COX)-2 in IL-1β plus β-amyloid [25-35] fragment (A)-stimulated human astrocytoma cell line U373MG. JST alone had no effect on the cell viability. The production of IL-6 and IL-8 was significantly inhibited by pretreatment with JST (1mg/㎖) on IL-1β plus A-stimulated U373MG cells. Maximal inhibition rate of IL-6 and IL-8 production by JST was about 41.22% (P<0.01) and 34.45% (P<0.05), respectively. The expression level of COX-2 protein was up-regulated by IL-1β plus A but the increased level of COX-2 was inhibited by pretreatment with JST (1 mg/㎖). These data indicate that JST has a regulatory effect on cytokine production and COX-2 expression, which might explain it's beneficial effect in the treatment of AD.