• Title/Summary/Keyword: PGE2

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Prostaglandin $E_1$ Increases cGMP Levels in Beating Rabbit Atria: Lack of Effects of $PGE_1$-induced Cyclic Nucleotides on Secretory and Contractile Functions

  • Jin, Xuan Shun;Quan, He Xiu;Kim, Sun-Young;Park, Sung-Hun;Kim, Sung-Zoo;Lee, Ho-Sub;Cho, Kyung-Woo
    • The Korean Journal of Physiology and Pharmacology
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    • v.11 no.5
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    • pp.175-182
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    • 2007
  • Members of prostaglandin(PG) E-series elicit cellular effects mainly through adenylyl cyclase-cAMP signaling. The role of $PGE_2$-induced increase in cAMP has been shown to be compartmentalized in the cardiac myocytes: $PGE_2$-induced increase of cAMP is not involved in the control of cardiomyocytic contraction. The purpose of the present study was to define the effect of $PGE_1$ on the cGMP levels and the role of $PGE_1$ in the atrial secretory function. Experiments were performed in perfused beating rabbit atria and atrial contractile responses, cGMP and cAMP efflux, and atrial natriuretic peptide(ANP) secretion were measured. $PGE_1$ increased cGMP as well as cAMP efflux concentration in a concentration-dependent manner, however, no significant changes in atrial secretory responses were observed(with $1.0{\mu}M\;PGE_1$; for cGMP, $144.76{\pm}37.5%$, n=11 versus $-16.81{\pm}4.76%$, n=6, control, p<0.01; for cAMP, $187.60{\pm}41.52%$, n=11 versus $7.38{\pm}19.44%$, n=6, control, p<0.01). $PGE_1$ decreased atrial dynamics slightly but transiently, whereas $PGE_2$ showed similar effects but with lower potency. Isoproterenol increased atrial cAMP efflux(with 2.0 nM; $145.71{\pm}41.89$, n=5 versus $7.38{\pm}19.44%$, n=6, control, p<0.05) and mechanical dynamics and decreased ANP secretion. The $PGE_1$-induced increase in cGMP efflux showed a bell-shaped concentration-response curve. $PGE_1$-induced increase of cGMP efflux was not observed in the presence of L-NAME, an inhibitor of nitric oxide(NO) synthase, or ODQ, an inhibitor of NO-sensitive guanylyl cyclase. L-NAME and ODQ showed no significant effect on the $PGE_1$-induced transient decrease of atrial dynamics. These data indicate that $PGE_1$ increases cGMP levels via NO-soluble GC signaling in the cardiac atrium and also show that $PGE_1$-induced increases in cGMP and cAMP levels are not involved in the regulation of atrial secretory and contractile functions.

Inhibitory Effect of Mixture of Ethanol Extracts in Agastachis Herba and Pueraria Radix on the Proliferation and $PGE_2$ Production of HT-29 Human Colon Cancer Cell Line (곽향과 갈근 복합제제의 대장암 세포주 HT-29 증식 저해효과 및 $PGE_2$ 생성 억제효과)

  • Lee, Seung-Youn;Kim, Hee-Seok;Kim, Jeoung-Ok;Hwang, Sung-Wan;Hwang, Sung-Yeoun
    • Korean Journal of Pharmacognosy
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    • v.37 no.4 s.147
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    • pp.283-289
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    • 2006
  • Ethanol extracts of the whole herb of Agastachis Herba (A) and of Pueraria Radix (P) alone and of their mixture (A+P) downregulated the cell growth, cyclooxygenase-2 (COX-2) expression, prostaglandin $E_2\;(PGE_2)$, and cGMP production. A, P, and A + P inhibited the cell growth of HT-29 colon cancer cells in a concentration- and time-dependent manner but not the growth of normal colon cell, CCD-112CoN. In addition, they markedly inhibited the productions of $PGE_2$ and cGMP as well as the mRNA expression of COX-2. These data suggest that non-toxic concentration of A, P, and A + P have a significant effect on the in vitro growth of HT-29 cells, specifically through the inhibition of the $PGE_2$ production via COX-2.

Analgesic Activity and Inhibitory Effect of PG Degradation, iNOS and $PGE_2$ by Ethyl Acetate Fraction of Angelica Koreana Radix (강활 에틸아세테이트 분획에 의한 PG 분해, iNOS, $PGE_2$, 활성 억제 및 진통효과)

  • Kim Si-Na;Lee Hyun-Ji;Lee Eun-Jeong;Nam Gyeong-Sug;Kim Hee-Seok;Hwang Sung-Wan;Hwang Sung-Yeoun
    • YAKHAK HOEJI
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    • v.50 no.2
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    • pp.99-104
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    • 2006
  • Prostaglandins biosynthesis and nitric oxide production have been implicated in the process of inflammation. In this study we investigated on the effects of ethyl acetate extract of Angelica Koreana Radix (EAKR) on the activities of prostaglandin $E_2\;(PGE_2)$, proteoglycan (PG) degradation and nitric oxide synthase (NO) in inflammation cytokines-activated rabbit articular chondrocytes. EAKR exhibited inhibitory activities on NO production and $PGE_2$ production as $73.08\%\;and\;89.49\%$, respectively at $20{\mu}g/ml$ and inhibited the degradation of PG in a concentration-dependent manner Zelatin zymography analysis demonstrated that EAKR significantly inhibited MMP-2, 9 expression in chondrocytes. In vivo, EAKR was shown to have inhibitory effects on acetic acid-induced pain. This study suggests that modulation of $PGE_2$, NO, PG degradation and MMP-2, 9 by EARK may be important in the prevention of inflammation and osteroarthritis.

NFATc Mediates Lipopolysaccharide and Nicotine-Induced Expression of iNOS and COX-2 in Human Periodontal Ligament Cells (사람 치주인대세포에서 Lipopolysaccharide와 니코틴으로 유도된 iNOS와 COX-2 발현에 NFATc의 관여)

  • Lee, Sang-Im;Yu, Ji-Su
    • Journal of dental hygiene science
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    • v.15 no.6
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    • pp.753-760
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    • 2015
  • Although nuclear factor of activated T cell (NFAT) plays a key role in inflammation, its anti-inflammatory effects and mechanism of action in periodontitis are still unknown. This study aimed to identify the effects of NFAT on the proinflammatory mediators activated by lipopolysaccharide (LPS) plus nicotine stimulation in human periodontal ligament cells (hPDLCs). The production of nitric oxide (NO) and prostaglandin $E_2(PGE_2)$ was evaluated using Griess reagent and an enzyme immunoassay, respectively. The expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2) and NFAT proteins was evaluated by Western blot analysis. LPS plus nicotine synergistically induced the production of NO and $PGE_2$ and increased the protein expression of iNOS, COX-2 and NFAT. Treatment with an NFAT inhibitor blocked the LPS plus nicotine-stimulated NO and $PGE_2$ release as well as the expression of iNOS and COX-2. Our data suggest that the LPS plus nicotine-induced inflammatory effects on hPDLCs may act through a novel mechanism involving the action of NFAT. Thus, NFAT may provide a potential therapeutic target for the treatment of periodontal disease associated with smoking and dental plaque.

Effect of Synthetic PGE-AcAm on the Reaction Rate of Epoxy System (합성된 PGE-AcAm이 에폭시 수지 계의 반응속도의 미치는 영향)

  • Lee, Jae-Yeong;Sim, Mi-Ja;Kim, Sang-Uk
    • Korean Journal of Materials Research
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    • v.6 no.6
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    • pp.644-650
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    • 1996
  • Diglycidy1 ether of bisphenol A (DGEBA)/4,4'-methylene dianiline(MDA)계의 경화반응 속도에 미치는 pheny1 glycidy1 ether (PGE)-acetamide(AcAm)의 영향을 연구하였다. 반응성 첨가제로 사용된 PGE-AcAm는 PGE와 acetamide를 2:1의 몰 비로 혼합한 후 18$0^{\circ}C$에서 1시간 반응시켜서 합성하였으며, PGE의 에폭사이드기와 AcAm의 아민기가 반응함으로써 수산기를 형성함에 의해 진행되었다. 이 때 생성된 수산기는 DGEBA와 MDA의 반응에서 촉매로 작용하여 반응속도를 크게 활성화 에너지는 11.11 Kcal/mol이었고, 30 phr의 PGE-AcAm이 첨가된 계의 활성화 에너지는 7.91Kcal/mol이었다.

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Fucoidan Suppresses Prostaglandin E2 Production and Akt Activation in Lipopolysaccharide-Stimulated Porcine Peripheral Blood Mononuclear Cells

  • Park, Geon-Tae;Ahn, Changhwan;Kang, Byeong-Teck;Kang, Ji-Houn;Jeung, Eui-Bae;Yang, Mhan-Pyo
    • Journal of Veterinary Clinics
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    • v.34 no.3
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    • pp.172-177
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    • 2017
  • Fucoidan, a cell wall polysaccharide found in the brown seaweed, is reported to have broad-spectrum biological activities. The objectives of this study were to examine the effect of fucoidan on prostaglandin $E_2$ ($PGE_2$) and cyclooxygenase-2 (COX-2) expression in lipopolysaccharide (LPS)-stimulated porcine peripheral blood mononuclear cells (PBMCs) and to determine whether these effects are involved in Akt activation. The levels of $PGE_2$ production in the culture supernatants from PBMCs were determined by the enzyme-linked immunosorbent assay (ELISA) kit and the levels of COX-2 mRNA were measured by real time polymerase chain reaction (RT-PCR). Akt activity was determined by Western blot analysis. Fucoidan in LPS-$na{\ddot{i}ve}$ PBMCs has no effect on $PGE_2$ production and COX-2 mRNA expression. Furthermore, fucoidan does not affect Akt activation in LPS- $na{\ddot{i}ve}$ PBMCs. However, $PGE_2$ production and COX-2 mRNA expression on PBMCs were remarkably enhanced by LPS stimulation. Akt activity was also increased by LPS. Increasing effects of $PGE_2$ production and COX-2 mRNA expression in PBMCs induced by LPS were suppressed by addition of fucoidan. In addition, fucoidan reduced an increase in Akt activity in LPS-stimulated PBMCs. These results suggested that fucoidan exerts potent anti-inflammatory properties by suppression of $PGE_2$ production, COX-2 mRNA expression and Akt activation in LPS-stimulated PBMCs.

Production of $PGE_2$ and $H_2O_2$ from Alveolar Macrophage Stimulated by Silica (유리규산에 의하여 자극된 폐포 대식세포의 $H_2O_2$$PGE_2$ 생성)

  • Lee, Seong-Beom;Choi, Moon-Ju;Park, Won-Sang;Lee, Jung-Yong;Chae, Gue-Tae;Kim, Sang-Ho;Kim, Choo-Soung
    • Tuberculosis and Respiratory Diseases
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    • v.41 no.5
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    • pp.513-520
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    • 1994
  • Background: The pathogenesis of silicosis has been focused on the interaction between alveolar macrophages and silica particle. Although fibrosis in silicosis has been studied extensively, the mechanism is still not fully understood. There is increasing evidence that monokines and arachidonic acid metabolites macrophage are involved in pathogenesis of silicosis. Recently, it was reported that prostaglandin E2 produced from macrophage counteracts the stimulatory effects of other monokines on fibroblast proliferation or collagen production. Until now, it was remained uncertain by which mechanism silica particle may activate alveolar macrophage to an enhanced release of prostaglandin E2. Methods: In order to investigate the relationship between the activity of alveolar macrophage and the production of $PGE_2$ from activated alveolar macrophage, the authors measured hydrogen peroxide and $PGE_2$ from alveolar macrophages activated by silica in vitro and from alveolar macrophages in the silicotic nodules from rat. Experimental silicosis was induced by intratracheal infusion of silica($SiO_2$) suspended in saline(50 mg/ml) in Sprague-Dawley rats. Results: produced by 1) The silicotic nodules with fibrosis were seen from the sections of rat lung at 60 days after intratracheal injection with 50 mg aqueous suspension of silica(Fig. 1). 2) In vitro, silica caused the dose dependent increase of hydrogen peroxide(p<0.05, Fig. 2A) and $PGE_2$(p>0.05, Fig. 2B) release from alveolar macrophages. Alveolar macrophages from rat with silicotic nodules released more hydrogen peroxide and $PGE_2$ than those of control group(p<0.05, Fig. 3). Conclusion: These results suggest that silica particle could activate macrophage directly and enhanced the release of $PGE_2$ and hydrogen peroxide from the alveolar macrophage.

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THE CONCENTRATIONS OF PROSTAGLANDIN E2, 6-KETO-PROSTAGLANDIN F1α, AND LEUKOTRIENE B4 IN PULPAL AND PERIAPICAL LESIONS (치수 및 치근단병소에서 Prostaglandin E2, 6-keto-Prostaglandin F1α, Leukotriene B4의 분포에 관한 연구)

  • Shon, Won-Jun;Baek, Seung-Ho;Lim, Sung-Sam
    • Restorative Dentistry and Endodontics
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    • v.25 no.2
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    • pp.193-201
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    • 2000
  • Prostaglandins (PGs) and Leukotrienes (LTs) have been implicated in the genesis of pulpal and periapical inflammation. In this study, the relationships among $PGE_2$, 6-keto-PG $F_1{\alpha}$ (a stable metabolite of $PGI_2$) and $LTB_4$ concentrations in inflamed pulp and periapical lesions were discussed. Pulp tissue were obtained in routine endodontic treatment and periapical lesions in periapical surgery after clinical diagnoses were made. These specimens were divided into four groups as normal pulp group (Control group), acute pulpitis group, chronic pulpitis group, and periapical lesion group. Pulp tissue and periapical lesions were stored in liquid nitrogen. The concentration of $PGE_2$, $PGI_2$ and $LTB_4$ were measured with ELISA. The data were analyzed by one-way ANOVA. Significantly higher levels of $PGE_2$, 6-keto-PG $F_1{\alpha}$ a and $LTB_4$ were found in acute pulpitis group than chronic pulpitis group and periapical lesion group(p<0.05). Periapical lesion group showed significantly higher mean concentrations of $PGE_2$ and $LTB_4$ than chronic pulpitis group. In control and chronic pulpitis group, significant higher levels of $PGI_2$ than $PGE_2$ and $LTB_4$ were found. These results suggested that the high levels of $PGE_2$ and $LTB_4$ in periapical lesions may be due to rich endothelium., fibroblast and lymphocyte known as the main producers of $PGE_2$ and $LTB_4$. $PGI_2$ may be thought to one of the most abundant PGs in normal pulp tissue.

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External Lyogel Formulation of Prostaglandin E1 Ethyl Ester (프로스타글란딘 E1 에칠에스테르의 외용 리오겔 제제 설계)

  • Yang, Sung-Woon;Lee, Jin-Kyo;Lee, Ji-Eun;Kim, Hee-Kyu;Park, Hye-Sook;Kim, Jong-Seok;Choi, Han-Gon;Yong, Chul-Soon;Choi, Young-Wook
    • Journal of Pharmaceutical Investigation
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    • v.34 no.2
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    • pp.107-114
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    • 2004
  • External lyogels containing prostaglandin $E_1$ ethyl ester $(PGE_1-EE)$, a prodrug of prostaglandin $E_1\;(PGE_1)$ as a therapeutic agent for erectile dysfunction, were formulated to overcome the aqueous instability and enhance the percutaneous absorption. Lyogels of $PGE_1-EE$ were prepared with ethanol (EtOH)/proplyene glycol (PG) cosolvent system as a vehicle, cineol as an enhancer, and hydroxypropylcellusose as a gelling agent. In vitro percutaneous absorption studies were performed to determine the rate of $PGE_1$ absorption through rat or hairless mouse skin. The permeability of $PGE_1-EE$ lyogel with enhancer was 16-fold greater than that of lyogel without enhancer. Cosolvent produced 9-fold increase in percutaneous absorption. Pharmacodynamic effects of lyogels were evaluated in mature male cats in terms of intracavernosal pressure (ICP). Lyogels containing 0.1 % of $PGE_1-EE$ showed higher ICP compared to intraurethral preparation of $PGE_1$ (1 %) and enhancer-free control lyogel. The shelf-life $(t_{10%})$ of lyogel at refrigerated condition $(4^{\circ}C)$ was calculated as 928 days, which is 4.2 times longer than that of control hydrogel. As a result, $PGE_1-EE$ was formulated successfully to a lyogel system with a selective enhancer and cosolvent system for the topical delivery of $PGE_1$.

Evaluation of antitumor. hepatoprotective and antimutagenic potentials of Phellinus gilvus (Phellinus gilvus의 항암활성, 간보호 및 항돌연변이성에 대한 평가)

  • Kang, Eun-Hee;Kim, Kil-Soo;Park, Seung-Chun
    • Korean Journal of Veterinary Research
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    • v.48 no.1
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    • pp.17-26
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    • 2008
  • This study was carried out to evaluate the antitumor, hepatoprotective and antimutagenic activities on hot water extract of Phellinus gilvus (PGE). Growth of tumor in mice that were orally given $0.25,0.5,1.0,2.0g\;kg^{-1}$ dose of PGE was inhibited in a dose-dependent manner (p < 0.05). The hepatoprotective effect of PGE in the carbon tetrachloride ($CCl_4$)-intoxicated rats was studied. In $CCl_4$ + PGE group, PGE was orally administered with 100 mg/kg/day dose 7 days before the treatment of $CCl_4$. The serum activity of aspartate aminotransferase and alanine aminotransferase in $CCl_4$ + PGE group were decreased at a rate of 59.6% and 54.1% compared with those in $CCl_4$ group, respectively (p < 0.05). Also, total cholesterol and triglyceride in $CCl_4$ + PGE group were significantly decreased at a rate of 90% and 73.6% compared with those in $CCl_4$ group (p < 0.05). In the Ames test, we confirmed PGE doesn't have any activity as a mutant, and PGE showed inhibitory effect against mutagenesis induced by 2-amino fluride and sodium azide in Salmonella typhimurium TA98, TA100 and TA1535 in a dose-dependent manner. From the above results, we may suggest that PGE might have useful as a material for functional food and/or animal pharmaceutics.