• Journal of Life Science
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• v.28 no.12
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• pp.1516-1522
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• 2018

Atherosclerosis is an obstructive vessel disease mainly caused by chronic arterial inflammation to which the proliferation and migration of vascular smooth muscle cells (VSMCs) is the main pathological response. In the present study, the primary responsible inflammatory cytokine and its signaling pathway was investigated. The proliferation and migration of VSMCs was significantly enhanced by the prostaglandin $F_{2{\alpha}}$ ($PGF_{2{\alpha}}$), while neither was affected by tumor necrosis factor ${\alpha}$. Prostacyclin $I_2$ was seen to enhance the proliferation of VSMCs while simultaneously suppressing their migration. Both prostaglandin $D_2$ and prostaglandin $E_2$ significantly enhanced the migration of VSMCs, however, proliferation was not affected by either of them. The proliferation and migration of VSMCs stimulated by $PGF_{2{\alpha}}$ progressed in a dose-dependent manner; the $EC_{50}$ value of both proliferation and migration was $0.1{\mu}M$. VSMCs highly expressed the phospholipase isoform $C-{\beta}3$ ($PLC-{\beta}3$) while others such as $PLC-{\beta}1$, $PLC-{\beta}2$, and $PLC-{\beta}4$ were not expressed. Inhibition of the PLCs by U73122 completely blocked the $PGF_{2{\alpha}}$-induced migration of VSMCs, and, in addition, silencing $PLC-{\beta}3$ significantly diminished the $PGF_{2{\alpha}}$-induced proliferation and migration of VSMCs. Given these results, we suggest that $PGF_{2{\alpha}}$ plays a crucial role in the proliferation and migration of VSMCs, and activation of $PLC-{\beta}3$ could be involved in their $PGF_{2{\alpha}}$-dependent migration.

• Korean Journal of Acupuncture
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• v.21 no.2
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• pp.125-137
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• 2004

Objectives : Recently, Herbal-acupuncture therapeutics has been used for the treatment of inflammatory diseases such as rheumatoid arthritis. Especially, we have been interested in chemical mediators concerned with inflammation such as prostaglandin, cytokine, nitrous oxide. The purpose of this study is investigated that the effect of Chelidonii Herbal-acupuncture solution in lipopolysaccharide-stimulated RAW 264.7 macrophages, performed several expeimental items : those are prostaglandin $E_2$, nitric oxide and cyclooxygenase-2. Methods : The cytotoxicity of Chelidonii Herbal-acupuncture solution in RAW 264.7 macrophages were measured by MTT-based cytotoxicity assay. In order to observe cyclooxygenase-2 mRNA expression in lipopolysaccharide-stimulated RAW 264.7 macrophages, RT-PCR was used. Prostaglandin $E_2$ formation and nitric oxide production was measured by competitive enzyme immunoassay and Griess assay. Results : 1.The MTT assay demonstrated that cytotoxic effect of Chelidonii Herbal-acupuncture solution in RAW 264.7 macrophages were not appeared before concentration of 1mg/ml. 2.Chelidonii Herbal-acupuncture solution inhibited cyclooxygenase-2 mRNA expression in lipopolysaccharide-stimulated RAW 264.7 macrophages. 3. Chelidonii Herbal-acupuncture solution inhibited nitric oxide production in lipopolysaccharide-stimulated RAW 264.7 macrophages. 4. Chelidonii Herbal-acupuncture solution inhibited prostaglandin $E_2$ formation in lipopolysaccharide-stimulated RAW 264.7 macrophages. Conclusions : On the basis of these results, It was shown that Chelidonii Herbal-acupuncture solution is significantly able to inhibit the production of $PGE_2$ and NO, as well as COX-2 mRNA expression. Our results may provide new mechanism by which Chelidonii Herbal-acupuncture solution accounts for its beneficial effect on accelerating wound healing and anti-inflammation.

• Journal of Applied Biological Chemistry
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• v.66
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• pp.114-121
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• 2023

Selective cyclooxygenase (COX)-2 inhibition is a novel strategy to reduce the risk of gastrointestinal side effects caused by conventional nonsteroidal anti-inflammatory drugs. However, some selective COX-2 inhibitors have become apparent to increase the risk of severe cardiovascular disease. The aim of this study was to examine the anti-inflammatory effect of rosemary extract (RE) and confirm the safety of cardiovascular side effects. Inhibition of COX enzyme activity was assessed, and the levels of COX-2 and prostaglandin E₂ (PGE₂) and COX-1 and thromboxane B₂ (TXB₂) were evaluated in lipopolysaccharide (LPS)-induced RAW 264.7 cells. The 40% RE group showed increased COX-2 inhibition activity in a dose-dependent manner, whereas the 50% RE group only exhibited at 100 ㎍/mL. In a cell-based study, COX-2 mRNA expression was similar in both RE groups and PGE₂ levels tended to decrease in the 40% RE group compared to the LPS group in the LPS pretreatment condition. In the LPS posttreatment condition, the COX-2 mRNA expression decreased in the 40% RE group, and PGE₂ levels were increased in the 40 and 50% RE groups. In both conditions, there was no significant difference in COX-1 and TXB₂ levels. In conclusion, 40 and 50% RE showed significant COX-2 inhibition, similar to the positive control group. It was confirmed that the inhibition of the COX-2 expression, but the effect did not affect the balance between prostacyclin and TXB₂. These results indicate that rosemary showed COX-2 inhibition activity with a low risk of cardiovascular diseases.

• The korean journal of orthodontics
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• v.13 no.2
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• pp.147-154
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• 1983

This experiment was performed to study the effect of $PGE_2$ on the bone resorption at the tooth movement by orthodontic force. The experimental animals were the Sprague-Dawley strain rats. The orthodontic force was applied by the insertion of separating clamp made of 0.014' (0.356mm) wire to the interproximal site between the 2nd and the 3rd upper right molars. In experiment I, $0.2{\mu}g,\;0.4{\mu}g,\;0.8{\mu}g,\;and\;1.0{\mu}g\;PGE_2$ were locally injected at the submucosa near the 2nd molar of the maxilla each. The effect was detected by the count of the number of osteoclasts appeared at the compressed surface of interradicular bone. In experiment II, 1.0 mg/kg indomethacin (a specificc inhibitor of prostaglandin synthetas.) was subcutaneously injected. The effect was examined by the count of the number of cateoclasts appeared at the compressed surface of interradicular bone. The obtained results were follows; 1. The number of osteoclasts on the compressed surface of the interradicular bone increased in proportion to the increased dosage of $PGE_2$ administered. The number of osteoclasts increased significantly at the administration of $0.8{\mu}g\;and\;1.0{\mu}g\;PGE_2$ in contrast to the control (P<0.05). 2. The administration of 1.0 mg/kg indomethacin decreased the number of osteoclasts at the compressed bony surface significantly (P<0.01).

• Journal of Animal Reproduction and Biotechnology
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• v.34 no.2
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• pp.75-85
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• 2019

Omega-3 α-linolenic acid and omega-6 linoleic acid are essential fatty acids for health maintenance of human and animals because they are not synthesized in vivo. The purpose of this study was to evaluate the effect of α-linolenic acid and linoleic acid supplementation on in vitro maturation and developmental potential of porcine oocytes. Various concentrations of α-linolenic acid and linoleic acid were added into in vitro maturation medium, and we evaluated the degree of cumulus expansion, oocyte nuclear-maturation rate, blastocyst rate, blastocyst quality, and levels of prostaglandin E₂, 17β-estradiol, and progesterone in the spent medium. High doses (100 μM) of α-linolenic acid and linoleic acid supplementation significantly inhibited cumulus expansion and oocyte nuclear maturation, and prostaglandin E₂ synthesis also significantly decreased compared with other groups (p < 0.05). Supplementation of 50 μM α-linolenic acid and 10 μM linoleic acid showed higher quality blastocysts in terms of high cell numbers and low apoptosis when compared with other groups (p < 0.05), and synthesis ratio of 17β-estradiol / progesterone also significantly increased compared with control group (3.59 ± 0.22 vs. 2.97 ± 0.22, 3.4 ± 0.28 vs. 2.81 ± 0.19, respectively; p < 0.05). Our results indicated that supplementation with appropriate levels of α-linolenic acid and linoleic acid beneficially affects the change of hormone synthesis (in particular, an appropriate increase in the 17β-estradiol / progesterone synthesis ratio) for controlling oocyte maturation, leading to improved embryo quality. However, high doses of α-linolenic acid and linoleic acid treatment results in detrimental effects.

• 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 Pharmacopuncture
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• v.14 no.3
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• pp.81-90
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• 2011

Objectives : Angelicae Gigantis Radix has been known traditional medicine with antimicrobial activities and it has been widely used for treatment of blood and inflammatory diseases. In the present study, some studies examined anti-inflammation effects of Angelicae Gigantis Radix but they usually were performed by ethanol extracted Angelicae Gigantis Radix pharmacopuncture. So We investigated the inhibitory effects of Angelicae Gigantis Radix pharmacopuncture by hot water and ethanol extract on Nitric oxide(NO) and Prostaglandin $E_2$($PGE_2$) production in lipopolysaccharide(LPS) induced macrophage cell. Methods : Angelicae Gigantis Radix was extracted by ethanol and hot water. Cell viability was determined by MTT assay. To evaluate anti-inflammation effects of Angelicae Gigantis Radix pharmacopuncture, we examined NO and $PGE_2$ production in LPS induced macrophages. The concentrations of NO and $PGE_2$ were measured by Griess assay and Enzyme Immuno-Assay. Results : 1) The MTT assay demonstrated that cytotoxic effect of Angelicae Gigantis Radix pharmacopuncture by hot water extract and ethanol extract in RAW 264.7 macrophage cells were not appeared. 2) Angelicae Gigantis Radix pharmacopuncture by ethanol extract and hot water extract inhibited NO production in LPS induced macrophages significantly. 3) Angelicae Gigantis Radix pharmacopuncture by ethanol extract tended to inhibiting $PGE_2$ production in LPS induced macrophages. And Angelicae Gigantis Radix pharmacopuncture by hot water extract inhibited LPS induced production of $PGE_2$ in RAW 264.7 macrophage cells significantly. Conclusions : This study suggests that Angelicae Gigantis Radix pharmacopuncture may have an anti-inflammatory property through the inhibition of NO and $PGE_2$ production in LPS induced macrophages. It may have a therapeutic potential for the treatment of various inflammatory diseases.

• Korean Journal of Food Science and Technology
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• v.42 no.6
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• pp.755-761
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• 2010

The quinone reductase (QR) inducing activities of mung bean and soybean solvent extracts were compared using murine hepatoma cells (Hepa 1c1c7). The mung bean extracts (ethylacetate and ethanol) showed higher chemoprevention index values (7.88-8.22) than those of soybean extracts (2.9-5.2) from four different cultivars. The mung bean extracts also had significantly higher inhibitory effects (47-62% at 100 ${\mu}g$/mL) than the soybean extracts (15-42% at 100 ${\mu}g$/mL) against the production of nitric oxide and prostaglandin E2 in lipopolysccharide stimulated macrophage RAW264.7 cells without cytotoxicity. Among seven recovered fractions of mung bean ethanol extract obtained by C 18 silica flash column chromatography, the most non-polar fraction exhibited the highest chemoprevention index of 10.4.

• Intestinal research
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• v.15 no.1
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• pp.75-82
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• 2017

Background/Aims: Cyclooxygenase-2 (COX-2), 15-hydroxyprostaglandin dehydrogenase (15-PGDH), and microsomal prostaglandin E synthase-1 (mPGEs-1) regulate prostaglandin $E_2$ ($PGE_2$) expression and are involved in colon carcinogenesis. We investigated the expression of $PGE_2$ and its regulating genes in sporadic human colon tumors and matched normal tissues. Methods: Twenty colonic adenomas and 27 colonic adenocarcinomas were evaluated. COX-2 and 15-PGDH expression was quantified by real-time polymerase chain reaction. The expression of $PGE_2$ and mPGEs-1 was measured using enzyme-linked immunosorbent assay and Western blotting, respectively. Results: The expression of COX-2, mPGEs-1, and $PGE_2$ did not differ between the adenomas and matched distant normal tissues. 15-PGDH expression was lower in adenomas than in the matched normal colonic tissues (P<0.001). In adenocarcinomas, mPGEs-1 and $PGE_2$ expression was significantly higher (P<0.001 and P=0.020, respectively), and COX-2 expression did not differ from that in normal tissues (P=0.207). 15-PGDH expression was significantly lower in the normal colonic mucosa from adenocarcinoma patients than in the normal mucosa from adenoma patients (P=0.018). Conclusions: Early inactivation of 15-PGDH, followed by activation of COX-2 and mPGEs-1, contributes to $PGE_2$ production, leading to colon carcinogenesis. 15-PGDH might be a novel candidate marker for early detection of field defects in colon carcinogenesis.

• Journal of People, Plants, and Environment
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• v.21 no.6
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• pp.485-492
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• 2018

This study aimed to develop and validate highly sensitive determination method of a prostaglandin ($PGE_1$, OP 1206) in human plasma by LC-MS/MS using column switching. Plasma stored at $-30^{\circ}C$ and treated with methanol effectively inhibited interferences synthesized post-sampling. Samples were added with internal standard and were separated by reversed-phase HPLC with a cycle time of 30min. The method was selective for OP 1206 and the regression models, based on internal standard, were linear across the concentration range 0.5-50 pg/mL with the limit of quantification of 0.5 pg/mL (limit of quantitation, LOQ) for OP 1206. The calibration curve of OP 1206 standards spiked in five individual plasma samples was linear ($r^2=0.9999$). Accuracy and precision at the concentrations of 0.5, 1.5, 5.0 and 40 pg/mL, and at the lower LOQ of 0.5 pg/mL were excellent at 20%. OP120 < 6 was stable in plasma samples for at least 24 hours at room temperature, 24 hours frozen at $-70^{\circ}C$, 24 hours in an auto sampler at $6^{\circ}C$, and for two freeze/unfreezing cycles. The validated determination method successfully quantified the concentrations of OP 1206 in plasma samples from simulated administrating a single $5{\mu}g$ OP 1206 formulation. Thus, this novel LC-MS/MS technique for drug separation, detection and quantitation is expected to become the standard highly-sensitive detection method in bioanalysis and to be applied to many low dose pharmaceutical products.