• Journal of Acupuncture Research
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• v.23 no.2
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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.

• Journal of Yeungnam Medical Science
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• v.23 no.1
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• pp.62-70
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• 2006

Background: Benign prostatic hyperplasia (BPH) is the most common benign tumor in older men; the etiology of this disease remains poorly understood. Testosterone and dihydrotestosterone (DHT) both act as androgen via a single androgen receptor. Testosterone is converted to DHT by $5{\alpha}$-reductase in prostatic stromal cells. Progesterone has been reported to inhibit DHT conversion; howevwe, its effect on prostatic stromal cells remains to be elucidated. Materials and Methods: In this experiment, we investigated the effect of progesterone on androgen receptor expression induced by DHT. We also tested the effect of progesterone on cyclooxygenase-2 (COX-2) expression, as well as prostate stromal cell proliferation using the cell count kit-8. Results: Progesterone did not cause an increase of prostate stromal cell proliferation. The mRNA expression of the androgen receptor and COX-2 were not changed by progesterone; the expressions of androgen receptor and COX-2 proteins were decreased by progesterone in prostate stromal cells. Conclusion: These results suggest that in prostate stromal cells, progesterone decreases androgen receptor protein expression, which results in decrement of COX-2 protein expression. This effect might be mediated by post-transcriptional regulation.

• Nutritional Sciences
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• v.6 no.1
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• pp.25-30
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• 2003

The effects of soy-isoflavones, which are phytoestrogens derived from plants with a flavonoid structure, on cyclooxygenase -2 (COX-2) expression, PGE2 production, and mapkinases expression, were investigated in experimentally-induced atherogenic rats by feeding a high fat-high cholesterol diet. Female Sprague-Dawley rats were bilaterally ovariectomized; sham-operated animals were used as controls. Three weeks later, the animals were randomized to the following treatments for an eight-week experimental period: 17$\beta$-estradiol (200$\mu$ g/kg diet), low concentration of isoflavones (0.8g/kg diet), and high concentration of isoflavones (4.0g/kg diet). In the group supplemented with a high dose of isoflavones, COX-2 expression was down-regulated. This down-regulation was accompanied by a reduced expression of pERK1/2. In the second experiment using 48-week old female Sprague-Dawly rats, the effects of isoflavones and estrogen were compared in the basal estrogen-supplementation at the level of 600$\mu$ g/kg diet. Isoflavones induced the marked down-regulation of COX-2 protein and the decrease in $PGE_2$ production in estrogen supplemented states and this was followed by the down-regulation of p38 among mapkinases. The two different mapkinases are involved in the down-regulation of COX-2 depending on estrogen-deficient and estrogen supplemented states. This kind of COX-2 down-regulation by isoflavones was not observed in the different tissue, mammary glands. Further investigations on the relationship between COX-2 and biological activities such as vasodilation by isoflavonesin the absence or the presence of estrogen ave required in vivo system of female rats.

• Journal of Acupuncture Research
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• v.20 no.2
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• pp.112-122
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• 2003

연구 배경 및 목적 : 봉독은 항염증 등의 효과를 가지고 있다고 알려져 있지만 세포 증식과 관련된 봉독의 효과에 대한 고찰을 위해 본 연구(硏究)에서는, 봉독(蜂毒) 약침(藥鍼) 자극(刺戟)이 아세트산 유발(誘發) 통각(痛覺) 과민증(過敏症)을 가진 쥐의 치상회(齒狀回)에서의 세포(細胞) 증식(增植)과 COX2 발현(發現)에 미치는 영향(影響)에 대해 알아보고자 하였다. 실험방법 : 대조군, 아세트산 처치군, 아세트산 0.1mg/kg 봉독 처치군, 아세트산 1mg/kg 봉독처치군(n=5 in each group)의 네 군으로 나누고 해당 군에 일벌 봉독(蜂毒)(Sigma Chemical Co., St. Louis, MO, USA)을 양측 족삼리 경혈(ST36)에 주입시키고 30분 후 아세트산(100% acetic acid 1% 용액의 0.5ml)을 복강내로 주입하여 복부 긴장 회수를 세었으며, BrdU 양성, COX 2 양성 세포수를 면역 화학 조직법을 수행하여 세어 보았다. 결과 : 아세트산 처치군에서는 대조군에 비해 5 bromo 2' deoxyuridine 양성 세포의 수는 감소(減少)되며, 치상회(齒狀回)에서의 COX 2의 발현(發現)은 증강(增强)되는 것으로 보여졌다. 봉독(蜂毒) 주입(注入)은 아세트산 유발(誘發) 복부(腹部) 긴장(緊張) 횟수와 치상회(齒狀回)에서의 COX2 발현(發現)을 억제(抑制)하여, 치상회(齒狀回)에서의 세포(細胞) 증식(增植)을 증가(增加)시켰다. 결론 : 이번 결과(結果)에서 보면, 치상회(齒狀回)에서의 COX 2의 발현(發現)은 세포(細胞) 증식(增植) 억제(抑制)와 관련(關聯)되며 봉독(蜂毒)은 COX 2 발현(發現) 억제(抑制)를 통해 치상회(齒狀回)에서의 새로운 세포(細胞) 형성(形成)을 증가(增加)시킨다는 것을 알 수 있다.

• Korean Journal of Clinical Laboratory Science
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• v.44 no.4
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• pp.229-238
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• 2012

Cyclooxygenase(COX-2) is an inducible enzyme that catalyzes the synthesis of prostaglandins (PGs) from arachidonic acid. Over-expression of COX-2 has been reported to be associated with progressive hepatic fibrosis in chronic hepatic C infection and rat liver fibrosis induced by carbon tetrachloride($CCl_4$). Recently, it is well known that mast cell products can stimulate the proliferation of hepatic stellate cells and key players in liver fibrosis. But little is known regarding their role in $CCl_4$-induced liver fibrosis in rat. Our aim was to investigate the relation between COX-2 expression and mast cells during liver fibrosis after $CCl_4$ treatment. Thirty Wistar rats were divided into five groups (non-treated 0, 2, 4, 6 and 8-week after $CCl_4$-treatment). Reverse transcription polymerase chain reaction (RT-PCR) and immunohistochemistry were used to assess the expression of ${\alpha}$-smooth muscle actin (${\alpha}$-SMA), collagen-1 and COX-2 in liver tissue from $CCl_4$-treated rats. The density of collagen and mast cells were determined using a computerized image analysis system in liver sections stained with picrosirius red and toluidine blue, respectively. The expression levels of ${\alpha}$-SMA, collagen-1 and COX-2 mRNA were significantly higher at 2 wk in $CCl_4$-treated groups than non-treated group. The number of mast cells in liver tissues increased gradually from 2 wk to 6 wk depending on the fibrosis severity but decreased abruptly at 8 wk. The significant increase of collagen-1 and ${\alpha}$-SMA mRNA expression in $CCl_4$-treated rats was continued until 6 wk while the COX-2 mRNA was significantly decreased at 8 wk. These results suggest that increased mast cells are closely associated with COX-2 over-expression during hepatic fibrogenesis of $CCl_4$-treated rats.

• Journal of the Korean Society of Food Science and Nutrition
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• v.35 no.9
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• pp.1115-1120
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• 2006

The effect of cinnamon ethanol extract (CN) on HT-29 cancer cell line has been examined. CN inhibited the growth of HT-29 colon cancer cells in a concentration and time dependent manner but not the growth of CCD-112CoN normal colon cells. And CN markedly inhibited the production of $PGE_2$ and cGMP as well as the mRNA expression of COX-2. These data suggest that non toxic concentration of CN has a significant inhibition effect on the growth of HT-29 cells, probably through the inhibition of $PGE_2$ production via COX-2 inhibition, and may have value as a safe chemopreventive agent for colon cancer.

• Korean Journal of Medicinal Crop Science
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• v.13 no.2
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• pp.75-79
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• 2005

Five coumarins, psoralen (1), scopoletin (2), isoimperatorin (4), (+)-marmesin (5) and xanthotoxin (6), three chromones, cimifugin (3), hamaudol (7) and sec-O-glucosylhamaudol (10), one sterol, daucosterol (8) and one aliphatic alcohol, galactitol (9) were isolated from the root of Peucedanum japonicum. Their chemical structures were identified by the physicochemical and spectroscopic data by comparing literature values. Among them, compounds 9 and 10 were isolated for the first time from this plant. The anti-inflammatory effects of isolated compounds were examined on cyclooxygenase (COX), compounds 1, 2 and 7 showed inhibitory activity on COX-1 with $IC_{50}$ values of 0.88, 0.27 and 0.30 mM, respectively. In the test for COX-2 activity, only compound 7 showed significant inhibitory activity with the $IC_{50}$ value of 0.57 mM. The other compounds exhibited weak inhibitory or no inhibitory activity.

• Journal of Life Science
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• v.16 no.4
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• pp.691-698
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• 2006

Phospholipase D (PLD) is known to play an important role in a variety of cells. However, little is known about $CoCl_2-mediated$ PLD signaling. In this study we demonstrated for the first time that $CoCl_2$ stimulates PLD activity and increases expression of cyclooxygenase-2 (COX-2), which is known to mediate inflammatory reaction. $CoCl_2-induced$ PLD activity was assessed by measuring the formation of $[^3H]$ phosphatidylbutanol (PtdBut), the product of PLD-mediated transphosphatidylation, in the presence of 1-butanol. To study mechanism of PLD signaling induced by $CoCl_2$, U87 human glioblastoma cells were stimulated by $CoCl_2$ and regulators of PLD activity induced by $CoCl_2$ were investigated using several inhibitors of signaling proteins. Moreover, PLD activation by $CoCl_2$ increased not only expression of COX-2 protein but also COX-2 promoter activity. In summary, these results suggest that $CoCl_2$ increases expression of COX-2 protein via PLD in human U87 glioblastoma cells.

• Natural Product Sciences
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• v.10 no.6
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• pp.315-320
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• 2004

Alpha-viniferin was previously isolated as a cyclooxygenase (COX)-2 inhibitor from Carex humilis (Cyperaceae) and is an oligomeric stilbene compound with benzofuran (BF) moieties in its chemical structure. In the present study, a chemically synthetic BF compound, named as 3,3-dimethyl-2,3,4,6,7,8,9,10,11,12,13,14,15,16,17,18-hexadecahydro-1H-benzo[b] cyclopentadeca[d]furan-1-one, was discovered to inhibit bacterial lipo polysaccharide (LPS)-induced prostaglandin $E_2$ $(PGE_2)$ production in macrophages RAW 264.7. The BF compound exhibited a selectively preferred inhibitory effect on COX-2 activity over COX-1 activity. Furthermore, BF compound inhibited LPS-induced COX-2 expression at transcription level. As a down-regulatory mechanism of COX-2 expression shown by BF compound, suppression of nuclear factor $(NF)-{\kappa}B$ activation has been demonstrated. BF compound inhibited LPS-induced $NF-{\kappa}B$ transcriptional activity and nuclear translocation of $NF-{\kappa}B$ p65, in parallel, but did not affect LPS-induced degradation of inhibitory ${\kappa}B{\alpha}$ protein $(I{\kappa}B{\alpha})$. Taken together, anti-inflammatory effect of BF compound on $PGE_2$ production was ascribed by its down-regulatory action on LPS-induced COX-2 synthesis in addition to inhibitory action on enzyme activity of COX-2.

• The Journal of Korean Obstetrics and Gynecology
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• v.20 no.3
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• pp.111-128
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• 2007

목적 : 이 연구는 천식, 기관지염, 폐렴, 결핵, 산후감모 등의 호흡기 질환에 사용되는 가미지황탕(加味地黃場)의 항염작용(抗炎作用)의 효과에 대해 알아보기 위해 시행되었다. 방법 : 가미지황탕(加味地黃場)의 항염작용(抗炎作用)의 효과를 평가하기 위해 세포독성에 미치는 영향, NO, $TNF-{\alpha}$, $IL-1{\beta}$, IL-6 생성량에 미치는 영향, $TNF-{\alpha}$, $IL-1{\beta}$, IL-6 유전자 발현에 미치는 영향, iNOS, COX-2 유전자 및 단백질 발현에 미치는 영향, $PGE_2$ 합성에 미치는 영향 및 COX-2, $NF-{\kappa}B$ 활성에 미치는 영향에 대한 실험평가를 하였다. 결과 : 가미지황탕(加味地黃場)은 MTT 분석을 통한 RAW 264.7 세포주의 생존력 평가에서 세포독성이 없었고, LPS로 유도된 RAW 264.7 세포주에서 NO, $TNF-{\alpha}$, $IL-1{\beta}$ 및 IL-6 생성량을 농도 의존적으로 억제하였다. 가미지황탕(加味地黃場)은 400 g/ml 농도에서 LPS로 유도된 RAW 264.7 세포주에 대해 $TNF-{\alpha}$, $IL-1{\beta}$ 및 IL-6 유전자 발현을 농도 의존적으로 억제하였고, LPS로 유도된 RAW 264.7 세포주에서 iNOS와 COX-2 유전자 및 단백질 발현은 농도 의존적으로 억제하였다. 또한 그 농도에 따라 $PGE_2$ 생성량이 현저하게 억제하였고, LPS로 유도된 COX-2 및 $NF-{\kappa}B$ 전사활성을 농도 의존적으로 억제함으로써 iNOS와 COX-2 유전자 발현을 억제하였다. 결론 : 이상의 실험을 통해 가미지황탕(加味地黃場)은 iNOS나 COX-2와 같은 Cytokine이 있는 효소에 의해 합성되고 천식에서 증가하는, 혈관과 기관지 긴장도와 관련 있는 NO와 $PGE_2$ 생성량을 억제하고, 염증과 관련된 $TNF-{\alpha}$, $IL-1{\beta}$, IL-6의 생성량을 억제하였다. 또한 $NF-{\kappa}B$ 활성을 억제함으로써 iNOS 및 COx-2 유전자 발현을 억제하였으므로 부인과 영역에 있어서도 산후감모, 만성해수 및 천식 등의 기관지의 염증질환에 응용할 수 있을 것으로 사료된다.