• 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.

• Archives of Plastic Surgery
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• v.32 no.3
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• pp.369-375
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• 2005

Apoptosis is a physiologic or programmed cell death process which is controlled by genes. It is essential for the function and the appropriate development of multicellular organism. It is also thought to be one of the main mechanisms of cell death in ischemic tissues. The effect of prostaglandin $E_1$($PGE_1$) is proven to be useful in the recovery of ischemic changes by inducing vasodilation of peripheral vessels and platelet disaggregation. $PGE_1$ is also known to suppress apoptosis in human liver sinusoidal endothelial cell from ischemia-reperfusion injury. The purpose of this study is to evaluate the effects of $PGE_1$ on the apoptosis in the ischemia reperfusion injury of rat intestine. Thirty Sprague-Dawley rats were used. In control group(N=15), superior mesenteric artery was occluded for 60 minutes and after removing the vessel clamp, it was reperfused for 60 minutes and harvested. In experimental group(N=15), a jejunal flap was also made as in the control group except for the intraarterial administration of the $PGE_1$ right after clamping the artery and removing the clamp. H&E, TUNEL and immunohistochemical stains for p53, bax, and bcl-2 were performed. There were ischemic changes in gross and microscopic findings in both groups. The apoptotic index was significantly lower in the experimental group($1.29{\pm}0.82$(p=0.003)) than in the control group ($2.33{\pm}0.95$). The rat intestinal ischemia apoptosis by ischemia-reperfusion was partly related to the modulating of bcl-2, bax, and p53 expression. Our results indicate that $PGE_1$ suppresses the apoptosis in the ischemic jejunal flap and this effect is probably the result of a increase in expression of bcl-2.

• Proceedings of the Korean Society of Applied Pharmacology
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• 2001.11a
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• pp.82-82
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• 2001

Previously, several prenylated flavonoids having a C-8 lavandulyl moiety were found to inhibit cyclooxygenase-1 (COX-1) as well as 5-lipoxygenase (5-LOX), and sophoraflavanone G was the most potent inhibitor against these eicosanoid generating enzymes among the prenylated flavonoids tested. In this investigation, effects of sophoraflavanone G on COX-2 induction from RAW 264.7 cells and in vivo inflammatory response were studied. Sophoraflavanone G inhibited prostaglandin E$_2$(PGE$_2$) production from lipopolysaccharide (LPS)-treated RAW cells by COX-2 down-regulation without significantly affecting COX-2 activity at 1 50 $\mu$M. Other prenylated flavonoids including kuraridin and sanggenon D also down-regulated COX-2 induction at 10-25 $\mu$M, lirhile kurarinone and echinoisoflavanone did not. In addition, sophoraflavanone G shelved in vivo anti-inflammatory activity against mouse croton oil-induced ear edema and rat carrageenan paw edema via oral (2-250mg/kg) or topical administration (10 - 250 $\mu\textrm{g}$/ear). Although the potencies of inhibition were far less than that of a reference drug, prednisolone, this compound showed higher anti-inflammato교 activity when applied topically, suggesting a potential use for several eicosanoid-related skin inflammation such as atopic dermatitis.

• Fisheries and Aquatic Sciences
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• v.24 no.12
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• pp.428-436
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• 2021

The aim of this study was to isolate and identify secondary metabolites from Sonchus brachyotus and evaluate their antioxidant and anti-inflammatory activities. In this study, we isolated three flavonoids from a 70% EtOH extract by Medium Pressure Liquid Chromatography (MPLC) and prep-High-Performance Liquid Chromatography (HPLC). To evaluate the biological activities (antioxidant and anti-inflammatory) of these flavonoids, their in vitro inhibitory activities against lipopolysaccharide (LPS)-induced reactive oxygen species (ROS) generation, nitric oxide (NO) production, and prostaglandin E₂ (PGE₂) secretion were determined. We successfully identified three flavonoids, namely luteolin (1), luteolin-7-O-β-D-glucoside (2), and luteolin-7-O-β-D-glucuronide (3) by spectral analyses. Luteolin (1) at 20 ㎍/mL inhibited ROS generation, NO production, and PGE₂ secretion by 48.6%, 61.28% and 12.10%, respectively, and luteolin-7-O-β-D-glucoside (2) inhibited NO and PGE₂ generation by 67.03% and 20.82%, respectively. Luteolin (1) and luteolin-7-O-β-D-glucoside (2) showed similar anti-inflammatory activities; however, luteolin (1) was observed to be a stronger antioxidant. Besides antioxidant and anti-inflammatory activities, S. brachyotus extract containing luteolin (1) and luteolin-7-O-β-D-glucoside (2) is considered to possess diverse biological activities. The results indicate that S. brachyotus is an edible medicinal plant, which is believed to be significant resource of functional foods.

• BMB Reports
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• v.56 no.6
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• pp.359-364
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• 2023

KAI1/CD82, a membrane tetraspanin protein, can prevent various cancers and retinal disorders through its anti-angiogenic and anti-metastatic capacity. However, little is known about its anti-inflammatory effect and molecular mechanism. Therefore, the present study aimed to inLPSvestigate effect of a recombinant protein of the large extracellular domain of human KAI1 (Gly 111-Leu 228, rhKAI1) on lipopolysaccharides (LPS)-stimulated RAW264.7 macrophage-like cells and mouse bone marrow-derived macrophages (BMDM) and to identify its underlying mechanism. Our data showed that rhKAI1 suppressed expression levels of classically macrophages (M1) phenotype-related surface markers F4/80+CD86+ in LPS-stimulated BMDM and RAW264.7 cells. In addition, LPS markedly increased mRNA expression and release levels of pro-inflammatory cytokines and mediators such as interleukin (IL)-1β, IL-6, tumor necrosis factor-α, cyclooxygenase-2, nitric oxide and prostaglandin E2, whereas these increases were substantially down-regulated by rhKAI1. Furthermore, LPS strongly increased expression of NF-κB p65 in the nuclei and phosphorylation of ERK, JNK, and p38 MAPK. However, nuclear translocation of NF-κB p65 and phosphorylation of JNK were greatly reversed in the presence of rhKAI1. Especially, rhKAI1 markedly suppressed expression of toll-like receptor (TLR4) and prevented binding of LPS with TLR4 through molecular docking predict analysis. Importantly, Glu 214 of rhKAI1 residue strongly interacted with Lys 360 of TLR4 residue, with a binding distance of 2.9 Å. Taken together, these findings suggest that rhKAI1 has an anti-inflammatory effect on LPS-polarized macrophages by interacting with TLR4 and down-regulating the JNK/NF-κB signaling pathway.

• Journal of Pharmaceutical Investigation
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• v.31 no.4
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• pp.281-287
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• 2001

Rebamipide is a novel anti-gastric ulcer agent that has been reported to increase the synthesis of mucus, to increase the mucosal concentration of prostaglandin, and to promote rapid ulcer healing. The purpose of the present study was to evaluate the bioequivalence of two rebamipide tablets, $Mucosta^{TM}$ (Otsuka Korea Pharmaceutical Co., Ltd.) and $Rebamide^{TM}$ (Kyung Dong Pharmaceutical Co., Ltd.), according to the guidelines of Korea Food and Drug Administration (KFDA). The rebamipide release from the two rebamipide tablets in vitro was tested using KP VII Apparatus II method at pH 6.8 dissolution media. Twenty normal male volunteers, $24.20{\pm}2.26$ years in age and $66.19{\pm}9.41\;kg$ in body weight, were divided into two groups and a randomized $2{\times}2$ cross-over study was employed. After one tablet containing 100 mg of rebamipide was orally administered, blood was taken at predetermined time intervals and the concentrations of rebamipide in serum were determined using HPLC method with fluorescence detector. The dissolution profiles of two rebamipide tablets were very similar at pH 6.8 dissolution media. Besides, the pharmacokinetic parameters such as $AUC_t$, $C_{max}\;and\;T_{max}$ were calculated and ANOVA test was utilized for the statistical analysis of the parameters. The results showed that the differences in $AUC_t$, $C_{max}\;and\;T_{max}$ between two tablets based on the $Mucosta^{TM}$ were -2.57%, 5.77% and -1.47%, respectively. Minimum detectable differences $({\Delta})$ at ${\alpha}=0.05$ and $1-{\beta}=0.8$ were less than 20% (e.g., 12.62% and 17.63% for $AUC_t,\;and\;C_{max}$, respectively). The powers $(1-{\beta})$ at ${\alpha}=0.05$, ${\Delta}=0.2$ for $AUC_t\;and\;C_{max}$ were above 99.00% and 88.56%, respectively. The 90% confidence intervals were within ${\pm}20%$ (e.g., $-9.96{\sim}4.82$ and $-4.54{\sim}16.09$ for $AUC_t\;and\;C_{max}$, respectively). Two parameters met the criteria of KFDA for bioequivalence, indicating that $Rebamide^{TM}$ tablet is bioequivalent to $Mucosta^{TM}$ tablet.

• Journal of Life Science
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• v.26 no.5
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• pp.537-544
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• 2016

Barley (Hardeum vulgare L.) sprout has received much attention in recent years as a functional food in many countries, especially in Korea and Japan. It has been reported that barley sprouts are comprised of 52.6% polysaccharides, 34.1% proteins, and 4.97% fats, along with a variety of vitamins, minerals, and polyphenols. The purpose of this study was to assess the anti-oxidant and anti-inflammatory activities of the ethanol extracts of barley sprouts. We examined the inhibitory effect of barley sprout extracts (BSE) on inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression, and nitric oxide (NO), prostaglandin E₂ (PGE₂) and cytokine production in lipopolysaccharide (LPS)-stimulated RAW 264.7 mouse macrophage cells. BSE contains high amounts of phenolics and flavonoids and exhibits potent anti-oxidative activity, as depicted by the DPPH radical-scavenging experiment. The concentration of total phenols was 17.55 μg/ml, and flavonoids, 13.98 μg/ml. We also investigated the anti-inflammatory activities of BSE in LPS-stimulated RAW 264.7 cells. Tumor necrosis factor-alpha and PGE₂ production, which had increased as a result of treatment with LPS, were significantly inhibited by BSE in a dose-dependent manner. BSE also significantly suppressed LPS-induced production of NO, and this was accompanied by a decrease in the expression of the iNOS and COX-2 proteins. These results indicate that barley sprouts may be a highly valuable natural product owing to its high-quality functional components as well as its anti-oxidant and anti-inflammatory activities.

• Archives of Plastic Surgery
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• v.37 no.6
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• pp.721-725
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• 2010

Purpose: The survival of composite graft is dependent on three steps, (1) plasmatic imbibitions, (2) inosculation, and (3) neovascularization. Among the many trials to increase the survival rate of composite graft, prostaglandin E1 (PGE1) has beneficial effects on the microcirculatory level with vasodilating, antithrombotic, anti-inflammatory and neoangiogenic properties. Lipo-PGE1 which is lipid microspheres containing PGE1 had developed to compensate the systemic and local side effects of PGE1. This study was proposed to determine whether Lipo-PGE1 administration enhanced the survival of composite graft through neovascularization quantitatively in a rabbit ear model. Methods: Fourteen New Zealand White Rabbits each weighing 3~4 kg were divided in two groups: (1) intravenous Lipo-PGE1 injection group and (2) control group. A $2{\times}1\;cm$ sized, full-thickness rectangular composite graft was harvested in each auricle. Then, the graft was reaaproximated in situ using a 5-0 nylon suture. For the experimental group, $3{\mu}g$/kg/day of Lipo-PGE1 ($5{\mu}g$/mL) was administered intravenously through the marginal vein of the ear for 14 days. The control group was received no pharmacologic treatment. On the 14th postoperative day, composite graft of the ear was harvested and immunochemistry staining used Monoclonal mouse anti-CD 31 antibody was performed. Neoangiogenesis was quantified by counting the vessels that showed luminal structures surrounded by the brown color-stained epithelium and counted from 10 random high-power fields (400x) by independent blinded observer. Statistical analysis (Wilcoxon Signed Ranks test for nonparametric data) was performed using SPSS v12.0, with values of p<0.05 considered significant. Results: The mean number of the microvessels was $15.48{\pm}8.65$ in the experimental group and $9.82{\pm}7.25$ in the control group (p=0.028). Conclusion: The use of Lipo-PGE1 facilitated the neoangiogenesis, resulted in the improvement of the survival rate of graft. On the basis of this results, we could support wider application of Lipo-PGE1 for more effective therapeutic angiogenesis and successful survival in various cases of composite graft in the human.

• Journal of Applied Biological Chemistry
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• v.60 no.4
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• pp.363-372
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• 2017

Hypericum ascyron has long been used as medicinal plant and recent studies reported that H. ascyron has anti-diabetic, anti-oxidant, and anti-bacterial effects. In this study, inhibitory effect from H. ascyron on pro-inflammatory responses has been investigated. H. ascyron was extracted at optimal extraction condition. Total phenolic contents in water and 90% ethanol were 29.75 and 31.82 mg/g, respectively. Hyaluronidase inhibitory activity of H. ascyron extracts ($50-200{\mu}g/mL$ phenolics) was 0.00-14.81% and 15.33-47.49%, respectively. In cell viability, cell toxicity was shown at concentration of $100{\mu}g/mL$ and $30{\mu}g/mL$ of water and 90% ethanol extract. Therefore, $10-50{\mu}g/mL$ in water extracts and $5-20{\mu}g/mL$ in ethanol extracts was selected each for further study. Inducible nitric oxide synthase (iNOS) derived nitric oxide (NO) and cyclooxygenase (COX)-2-derived prostaglandin $E_2$ ($PGE_2$) protein expression inhibitory effect of extracts were inhibited in a dose dependent manner, significantly. Also, the pro-inflammatory cytokines inhibitory effect such as tumor necrosis $factor-{\alpha}$, nterleukin (IL)-6 and $IL-1{\beta}$ were decreased in the dose dependent manner. The results indicate that H. ascyron extracts reduced inflammatory responses in lipopolysaccharide-induced 264.7 cells via the regulation of the iNOS, COX-2, NO, $PGE_2$, and pro-inflammatory cytokines. Therefore, H. ascyron extracts have significant anti-inflammatory effect and a source as therapeutic materials.

• Journal of Chest Surgery
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• v.30 no.10
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• pp.949-960
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• 1997

Background. Limited ischemic tolerance of the lung has remained one of the factors that limits the expansion of pulmonary transplantation as a treatment for end-stage pulmonary disease. Numerous studies on safe long term preservation for lung transplantation has been performed for the purpose of developing ideal preservation solution with extracellular type or intracellular type solutions. In this. study, we examined the efficacy of L DG solution in lung preservation longer than 20 hours by comparison with modified Euro-Collins solution. Iwethods. Thirty-(our adult mongrel dogs were divided into two groups. Donor lungs were flushed with LPDG solution(n=9) or modified Euro-Collins(MEC) solution(n=8) and stored for 24 hours at 1$0^{\circ}C$. All donor lungs were perfused through the pulmonary arteries with solutions containing prostaglandin El and verapamil. Left canine lung allotransplantations wereperformed. Assessment(hemodynamic indices and arterial blood gas analysis) of left implanted lung was made by occluding the right pulmonary artery for ten minutes using pulmonary artery Cuff. Assessment was repeated at the interval of 30 minutes, one hour, and two hours later after reperfusion and then chest X-ray, computed tomogram and lung perfusion scan were obtained. In survival dogs follow-up studies were done with assessment with chest X-ray, computed tomogram of the chest and lung perfusion scan on 7th day postoperatively. After preservation above 20 hours, pathological examinations for ultrastructural findings on right lung were performed in each group. Results. With respect to arterial oxygen tension, LPDG group was superior to MEC but there was no statistical significance for 2 hours after reperfusion. Mean pulmonary artery pressure was less increased(p < 0.05) and cardiac output higher(p <0.05) than MEC group until 2 hours after reperfusion. After 2 hours of reperfusion, both groups showed transplanted lung function deteriorated gradually. Perfusion scan of the transplanted lung in LPDG group showed better perfusion rate in immediate post-reperfusion, 3 days and 7 days later respectively but there was no statistical significance and corelation with PaO2 and computed tomoRravhic views. In scanning electron microscopy of pulmonary artery after preservation, LPDG group relatively shows less irregular protrusion of the inner surface of endothelial cell of poulmonary artery than MEC group. Conclusions, e concluded that LPDG solution can offer safe lung preservation above 20 hours with adequate immunosuppressive therapy and prevention of the infection.