• Biomolecules & Therapeutics
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• v.20 no.6
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• pp.520-525
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• 2012

Prostaglandin (PG) $E_2$, the most abundant prostaglandin in the human body, is synthesized from arachidonic acid via the actions of cyclooxygenase (COX) enzymes. $PGE_2$ exerts homeostatic, cytoprotective, inflammatory, and in some cases anti-inflammatory effects. Also, it has been reported that $PGE_2$ is involved in hair growth. Diphlorethohydroxycarmalol (DPHC) is a phlorotannin compound isolated from the brown algae Ishige okamurae, with various biological activities in vitro and in vivo. In this study, the biological effect and mechanism of action of DPHC on prostaglandin synthesis in HaCaT human keratinocytes was examined. The results showed that, in these cells, DPHC significantly and dose-dependently induced $PGE_2$ synthesis by increasing the protein and mRNA levels of COX-1 and COX-2. Interestingly, DPHC-induced COX-1 expression preceded that of COX-2. Also, while both rofecoxib and indomethacin inhibited $PGE_2$ production, the latter was seems to be the more potent. From above results, we can expect that DPHC has some beneficial effects via increasing of $PGE_2$ production.

• Biomolecules & Therapeutics
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• v.29 no.1
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• pp.64-72
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• 2021

Renal cell carcinoma (RCC) is likely to metastasize to other organs, and is often resistant to conventional chemotherapies. Thymoquinone (TQ), a phytochemical derived from the seeds of Nigella sativa, has been shown to inhibit migration and metastasis in various cancers. In this study, we assessed the effect of TQ on the migratory activity of human RCC Caki-1 cells. We found that treatment with TQ reduced the proteolytic activity of matrix metalloproteinase-9 (MMP-9) in Caki-1 cells. TQ significantly repressed prostaglandin E2 (PGE2) production, its EP2 receptor expression as well as the activation of Akt and p38, the wellknown upstream signal proteins of MMP-9. In addition, treatment with butaprost, a PGE2 agonist, also induced MMP-9 activity and migration/invasion in Caki-1 cells. Moreover, pharmacological inhibitors of PI3K/Akt and p38 remarkably attenuated butaprost-induced Caki-1 cell migration and invasion, implying that activation of PI3K/Akt and p38 is a bridge between the PGE2-EP2 axis and MMP-9-dependent migration and invasion. Taken together, these data suggest that TQ is a promising anti-metastatic drug to treat advanced and metastatic RCC.

• The Korea Journal of Herbology
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• v.30 no.6
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• pp.77-82
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• 2015

Objectives : This study was designed to investigate of the anti-inflammatory effects of Schisandra chinensis seed oil(SSO) on the production of pro-inflammatory substances in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages.Methods : SSO was measured the production of pro-inflammatory factor (NO, PGE2, IL-1β iNOS and, COX-2) in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. we used the following methods : cell viability assay, Griess reagent assay, enzyme-linked immunosorbent assay, Western blotting analysis.Results : The cell viability of SSO(0∼500 μl/mL) processing group was 96.9% and the processing of SSO didn't have an effect on the cytotoxicity. The inhibitory effect of the nitric oxide (no) production of SSO(500 μg/mL, 50 μg/mL, 10 μg/mL) was each 70.3%, 37.6% and 26.5%. IL-1β production inhibition ability of SSO(500 μg/mL, 100 μg/mL) was each 49.88% and 48.8%. PGE2 production inhibition ability of SSO(500 μg/mL, 100 μg/mL) was each 49.88% and 73.1%, 70.5%. By using SSO, it experimented about iNOS protein expression inhibition ability, that is the NO production enzyme. iNOS protein expression increased in the group processing LPS independently. iNOS protein expression decreased in the group processing SSO together. The expression of the COX-2 protein decreased 89.6%, 81.8% in the group processing SSO. The significance was in the relationship with NO formation inhibition with the relationship with the PGE₂ formation inhibition and iNOS protein, it confirmed in SSO with the COX-2 protein.Conclusions : Stimulation of the RAW 264.7 cells with LPS caused an elevated production of nitric oxide (NO), IL-1β and PGE₂ which was markedly inhibited by the pretreatment with SSO without causing any cytotoxic effects. The reduced expressions of iNOS protein were consistent with the reductions in NO production in the culture media. SSO may be useful for the treatment of various inflammatory diseases.

• Journal of Mushroom
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• v.19 no.3
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• pp.176-183
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• 2021

In this study, the anti-inflammatory activity of an extract of the fruiting body of the Tuber himalayense (TH) truffle collected from oak growing areas in Korea was investigated. The extract was not cytotoxic at concentrations below 100 ㎍/mL in an experiment evaluating inflammation inhibitory effect in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. LPS-induced nitric oxide (NO) and prostaglandin E2 (PGE₂) production was inhibited by the extract in a concentration-dependent manner. Western blot assay results indicated that the anti-inflammatory activity of TH extract was likely caused by the reduced production of NO and PGE₂ via suppression of induced NO synthase and cyclooxygenase-2 gene expression. In addition, TH extract effectively inhibited the production of interleukin (IL)-1β and IL-6 by macrophages. Thus, TH extract effectively inhibits the overexpression of various inflammatory mediators and could be valuable in formulating anti-inflammatory foods and medicines that target these components.

• Journal of Life Science
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• v.30 no.3
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• pp.278-284
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• 2020

Magnolia kobus is known to exert various biological effects, such as antioxidant and hypnotic activity. In this study, we investigated the antimicrobial and anti-inflammatory activity of M. kobus essential oil extracted using steam distillation. Its antimicrobial activity was tested against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa by the paper disk diffusion and minimum inhibitory concentration (MIC) methods. Its anti-inflammatory activity was evaluated by measuring its inhibition ratio on the production of nitric oxide (NO) and PGE₂ in lipopolysaccharide (LPS)-induced RAW264.7 cells. Its composition was analyzed by gas chromatography-mass spectrometry (GC-MS). The results showed that M. kobus essential oil exhibited excellent antibacterial activity against S. aureus, with a clear zone of 18 mm and an MIC value of 0.25 mg/ml. Its clear zones against P. aeruginosa and E. coli were 14 mm and 17 mm, respectively, while its MIC values were 1 mg/ml and 0.5 mg/ml, respectively. The essential oil exhibited no cytotoxicity to the RAW264.7 cells at a concentration of 500 ㎍/ml while showing NO (37.7%) and PGE₂ inhibition (24.0%). Its three main fragrance ingredients identified were 3-carene (77.07%), β-elemene (6.92%), and caryphyllene (2.86%). The results suggest that M. kobus essential oil has potential as a cosmetic functional material with antimicrobial and anti-inflammatory effects.

• Journal of the Korean Applied Science and Technology
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• v.39 no.5
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• pp.644-651
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• 2022

The skin is the largest organ of the human body and protects the inside of the body. Ultraviolet rays cause various inflammatory reactions in the skin, including photoaging and oxidative damage. The purpose of this study is to investigate the protective effect of Saponaria extract by irradiating UVB on fibroblasts. In this study, the effectiveness of Saponaria showing protective activity against UVB-induced cytotoxicity, oxidative cell death, and NO and PGE₂ production was evaluated. HS68 cells were irradiated with UVB(120 mJ/cm²) and treated with Saponaria extract at various concentrations of 100, 200, and 400 ㎍/mL for 24 hours. Intracellular reactive oxygen species (ROS) generated by ultraviolet B were detected using a spectrofluorometer after DCF-DA staining. Lipid peroxidation was also analyzed by measuring the level of 8-isoprostane secreted into the culture medium. As a result, treatment with Saponaria extract effectively inhibited UVB-induced cytotoxicity. Oxidative cell damage was mediated by PGE₂ in UVB-induced HS68 fibroblasts, which was significantly inhibited by Saponaria extract treatment. In addition, it was evaluated that the protective effect of these extracts was mediated by the inhibition of intracellular ROS production and lipid peroxidation in a concentration-dependent manner. These results suggest that Saponaria extract can be used as an anti-aging functional material because it inhibits skin damage mediated by oxidative stress caused by UVB and exhibits a cellular protective effect.

• BMB Reports
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• v.33 no.2
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• pp.184-187
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• 2000

Prostaglandin $E_2$ ($PGE_2$) plays an important role in the regulation of various gastric functions, and the growth-inhibitory activities on tumor cells are studied in vitro and in vivo. Although the mechanisms have attracted many researchers in the past decade, the molecular mechanisms of cell cycle arrest, or induction of apoptosis by $PGE_2$, is unclear. We investigated the effects of $PGE_2$ on the growth of the human gastric carcinoma cell line SNU1 and genes that are regulated by $PGE_2$ and isolated them using differential display RT-PCR (DD RT-PCR). FACS analysis suggested that SNU1 cells were arrested at the G1 phase by $PGE_2$ treatment. This growth inhibitory effect was in a time- and dose-dependent manner. Treatment of SNU1 cells with $10\;{\mu}g/ml$ $PGE_2$, followed by DD RT-PCR analysis, revealed differently expressed bands patterns from the control. Among the differently expressed clones, we found an unidentified cDNA clone (HGP-27) overexpressed in $PGE_2$-treated cells. The full-length cDNA of HGP-27 was isolated using RACE, which consisted of a 30-nt 5'-noncoding region, a 891-nt ORF encoding the 296 amino acid protein, and a 738-nt 3'-noncoding region including a poly(a) signal. This gene was localized on the short arm of chromosome number 11. Using the Motif Finder program, a myb-DNA binding repeat signature was detected on the ORF region. The COOH-terminal half was shown to have similarity with the $NH_3$-terminal domain of thioredoxin (Trx). This relation between HGP-27 and Trx implied a potential role for HGP-27 in modulating the DNA binding function of a transcription factor, myb.

• Biomolecules & Therapeutics
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• v.17 no.4
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• pp.418-421
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• 2009

Structural alterations of wogonin were conducted to observe the role of each functional group at the A-ring of wogonin on the inhibitory activities against COX-2 catalyzed $PGE_2$ production from LPS-induced RAW 264.7 cells. Serial deletion of the functional groups at the A-ring of wogonin exhibited low to comparable bioactivity. The present study validated that all the functional groups at the A-ring of wogonin are important factors to exhibit the optimum inhibitory activities.

• Journal of Applied Biological Chemistry
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• v.66
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• pp.46-52
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• 2023

The most abundant flavanone of grapefruits, naringenin (NN), is well known for its hepatoprotective, anti-lipid peroxidation and anti-carcinogenic effects. We generated three derivatives from NN using this technique in previous studies. Among them, it was confirmed that naringenin-7-O-phosphate (N7P), whose biological and physicochemical properties were not reported, showed a water solubility 45 times higher than that of NN. Therefore, in this study, the anti-inflammatory activity was evaluated in RAW 264.7 cells to investigate the potential physiological activity of N7P. As a result, N7P showed nitric oxide (NO) inhibitory activity at concentrations that did not show toxicity. In addition, prostaglandin E₂ (PGE₂) showed significant inhibitory activity from the lowest concentration of 12.5 μM and showed increased inhibitory activity compared to NN. In addition, as a result of western blot, N7P showed increased cyclooxygenase-2 (COX-2) inhibitory activity than NN, and effectively inhibited NO and PGE₂ by significantly inhibiting their expression pathways. N7P also inhibited inflammatory cytokines, including tumor necrosis factor-α, interleukin-6. Based on these results, we propose that N7P can be used as a potent antiinflammatory agent.

• Archives of Plastic Surgery
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• v.32 no.1
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• pp.5-11
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• 2005

Prostaglandin $E_1$($PGE_1$) is known to have various physiological action such as vasodilatation, decrease of blood pressure, angiogenesis, inhibition of platelet aggregation and so forth. $PGE_1$ has been developed in many different formulations in order to overcome its chemical instability and deactivation in the lungs when administered parenterally. Lipo-AS013 is a potent drug with higher chemical stability and greater vascular wall targeting than others. The study was done on $3{\times}10cm$ model flap of dorsal skin of Sprague-Dawley rats and the flap perfusion survival were observed and documented. The flap treated with Lipo-AS013 beforehand was given intravenously Sodium fluorescein 10 minutes later, and then Percent Dye Fluorescence Index(% DFI) was calculated. The results were compared to a control group and the group administered locally epinephrine.. In the control group, the % DFI and flap survival rate increased from $54.1{\pm}6.7$ to $65.0{\pm}2.6$(p<0.01) while in Lipo-AS013 group from $55.3{\pm}2.2$ to $67.4{\pm}1.9$(p<0.01), respectively. In the epinephrine group, the % DFI(p<0.05) and flap survival rate(p<0.001) decreased. In the both epinephrine and Lipo-AS013 group Percent DFI and flap survival rate are comparable with the control group.The result indicates that the potent Lipo-AS013 enhances the blood flow and flap survival. This highly potent Lipo-AS013 may have targeting ability and accumulate $PGE_1$ onto the vascular walls. A quantitative analysis of fluorescence on the skin surface is a reliable tool to measure the blood perfusion into an ischemic flap and its viability. Further comparative study with conventional $PGE_1$ and Lipo-$PGE_1$ is needed in order to clarify the action and efficiency of Lipo-AS013.