• Bulletin of the Korean Chemical Society
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• 제31권2호
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• pp.384-388
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• 2010

Human microsomal prostaglandin E synthase-1 (mPGES-1) catalyzes the conversion of prostaglandin $H_2$ ($PGH_2$) into prostaglandin $E_2$ ($PGE_2$). To establish a stable and efficient method to assess the activity of mPGES-1, a coupled enzyme assay system using mPGES-1, 15-hydroxyprostaglandin dehydrogenase (15-PGDH) and phosphomolybdic acid (PMA) was developed. In this assay system, $PGH_2$ was converted to $PGE_2$ by mPGES-1, and then $PGE_2$ was further transformed to the 15-keto-$PGE_2$ by 15-PGDH accompanying the production of NADH, which was easily detected by fluorescence spectrometry in a multi-well plate format. During the reaction, spontaneous oxidation of $PGH_2$ was prevented by PMA. Using this novel assay, the $K_m$ value of mPGES-1 for $PGH_2$ and the $IC_{50}$ value of the previously characterized inhibitor, MK-886, were determined to be 0.150 mM and $2.8\;{\mu}M$, respectively, which were consistent with the previously reported values. In addition, low backgrounds were observed in the multi-wall plate screening of chemical compounds.

• 동의생리병리학회지
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• 제20권2호
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• pp.455-459
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• 2006

The inhibitors of prostaglandin $E_2\;(PGE_2)$ production and cyclooxygenase-2 (COX-2) activity have been considered as potential anti-inflammatory agents. In this study, we evaluated 9 compounds isolated from 5 Korean phytomedicinal plants (Spirea prunifolia, Paeonia suffruticosa, Salvia miltiorrhiza, Scutellaria baicalensis, and Artemisia capillaris) for the inhibition of $PGE_2$production and COX-2 expession in lipopolysaccharide (LPS)-stimulated human macrophages U937 cells. As a result, several compound such as prunioside A, penta-O-galloyl-beta-D-glucose, tanshinone IIA, baicalin, baicalein, wogonin, scopolatin, scoparone and decursinol showed potent inhibition of $PGE_2$production (50-70% inhibition at the test concentration of $10\;{\mu}M$). In addition, these compounds were also considered as potential inhibitors of COX-2 activity (45-73% inhibition at the test concentration of $10\;{\mu}M$). These active compound mediating COX-2 inhibitory activities are warranted for further elucidation of active principles for development of anti-inflammatory agents and these properties may contribute to the anti-atopic dermatitis activity.

• Journal of Pharmaceutical Investigation
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• 제34권2호
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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 $PGE_1$.

• 한국약용작물학회지
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• 제22권6호
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• pp.457-462
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• 2014

Prostaglandin (PG) $E_2$ is an important mediator of skin wound healing without excessive scarring and gastric ulcer healing. However, $PGE_2$ has a short lifetime in vivo because it is metabolized rapidly by 15-hydroxyprostaglandin dehydrogenase (15-PGDH). Ethanol extract of Eriobotryae folium (EFEE) elevated intracellular and extracellular $PGE_2$ levels in HaCaT cells and inhibited 15-PGDH ($ED_{50}$ : $168.4{\mu}g/mL$) with relatively low cytotoxicity ($IC_{50}$ : $250.0{\mu}g/mL$). Real-time PCR analysis showed that mRNA expression of cyclooxygenase (COX)-1 and COX-2 enzymes were increased and prostaglandin transporter (PGT) was decreased in HaCaT cells by EFEE. Moreover, wound healing effect of EFEE ($168.4{\mu}g/mL$) was comparable to that of TGF-${\beta}1$ (300 pg/mL) as a positive control. These results demonstrate that EFEE may be valuable therapeutic materials for the treatment of $PGE_2$ level dependent diseases.

• Animal cells and systems
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• 제16권4호
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• pp.274-279
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• 2012

Thymoquinone (TQ), a drug extracted from the black seeds of Nigella sativa, has been shown to exhibit anti-inflammatory, anti-oxidant, and anti-neoplastic effects in numerous cancer cells. The effects of TQ on cyclooxygenase-2 (COX-2) expression and prostaglandin $E_2$ ($PGE_2$) production in MDA-MB-231, however, remain poorly understood. Western blot analysis and immunofluorescence staining were performed to study the expression levels of inflammation regulatory proteins in MDA-MB-231. $PGE_2$ assay was conducted to explore the TQ-induced production of $PGE_2$. In this study, we investigated the effects of TQ on COX-2 expression and $PGE_2$ production in MDA-MB-231. TQ significantly induced COX-2 expression and increased $PGE_2$ production in a dose-dependent manner, as determined by a Western blot analysis and $PGE_2$ assay. Furthermore, the activation of Akt and p38 kinase, respectively, was up-regulated in TQ treated cells. Inhibition of p38 kinase with SB203580 and PI3kinase (PI3K) with LY294002 abolished TQ-caused COX-2 expression and decreased $PGE_2$ production. These results collectively demonstrate that TQ effectively modulates COX-2 expression and $PGE_2$ production via PI3K and p38 kinase pathways in the human breast cancer cell line MDA-MB-231.

• 약학회지
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• 제52권1호
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• pp.85-91
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• 2008

8-Acyl and 8-sulfonylamidowogonin analogues were synthesized as potential anti-inflammatory agents. Nitration of 5,7-dihydroxyflavone (chrysin) followed by methylation of phenol groups and reduction of nitro group yielded 8-aminowogonin analogues. Acylation and sufonylation of 8-aminowogonin followed by demethylation reactions gave the title compunds. The synthesized wogonin analogues showed much reduced inhibitory activity on prostaglandin $E_2\;(PGE_2)$ production.

• Archives of Reconstructive Microsurgery
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• 제9권2호
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• pp.179-185
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• 2000

In the field of microsurgery, the vascular obstruction of the microvascular anastomosis by thrombus is one of the most important complication. The purpose of this study is to compare the effect between aspirin and prostaglandin $E_1$($PGE_1$) which act as the peripheral vasodilatation and platelet disaggregation. We have used total 48 white male rats and divided them into three gruoups(A, B and C group). Each group consists of 16 rats respectively. A group is as control, B group is medicated with aspirin(3.0mg/kg/day) and C group with $PGE_1(1.2{\mu}g/kg/day)$. The gross and histopathologic findings at anastomosed site were observed on 3, 5, 10 and 15 days after vascular anastomosis and the results were obtained as the followings. 1. The microvascular patency rate is 81.2% in control group, 93.8% in aspirin group and 100% in $PGE_1$ group. 2. On the histologic examination, the formation of mural thrombus is decreased both in the aspirin and $PGE_1$ group as comparing with the control group and also the hypertrophy of the intima forming from media is less formed in $PGE_1$ group than aspirin group and the degree of thickeness is also less. 3. The fibrosis of media is less observed in $PGE_1$ group than aspirin group. According to the above results, the application of $PGE_1$ to the microsurgery is considered to be effective on the prevention of the thrombus formation and on providing high patency rate.

• The Korean Journal of Pain
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• 제7권2호
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• pp.299-302
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• 1994

Prostaglandin E1(PGE1) is a potent vasodilator and is a useful drug for the treatment of occlusive peripheral vascular disease. It has been used systemically via intravenous route or regionally via intraarterial route. We tried intravenous regional administration of PGE1 for the treatment of a patient with occlusive arterial disease involving left fingers. During the 13th injection, the patient complained of severe pain at the injection site during the drug administration. Thereafter, the patient developed painful and severe swelling with blebs on his left hand. Systemic antibiotics were given together with stellate ganglion block of the affected left side. PGE1 was substituted to reserpine, which is subcutaneously injectable, for the second term treatment.

• 대한약리학회지
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• 제11권1호
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• pp.27-31
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• 1975

1. The isolated strips of guinea-pig, fowl and reptiles (snake and tortoise) showed consistenly excitatory responses to $PGE_1\;and\;E_2$, which were dose-dependent. 2. Frog intestine revealed inhibitory responses to both $PGE_1\;and\;PGE_2$ except a small of $PGE_2$ (1-10 ng/ml) caused slight contraction. 3. The intestines of pieces showed inconsistent responses to $PGE_1\;and\;E_2$. In fresh-water fish(carp), $PGE_1$ produced relaxation under the dose of 50 ng/ml, and contraction by the large doses, but $PGE_2$ consistently caused contraction in dose-dependent manner. However, the strips of sea-water fish revealed the different responses to PGE compound: $PGE_1$ caused relaxation and $PGE_2$ conversly contraction even though in small degree. 4. These results that there are genera differences in the responses of the longitudinal strips of intestine to $PGE_1\;and\;PGE_2$ was assumed to be possibly correlated with evolutionally primitive function of gut.

• 한국수산과학회지
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• 제50권1호
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• pp.41-47
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• 2017

Perhaps the most common type of reproductive dysfunction in captive fish is failure of females to undergo final oocyte maturation and thus to ovulate and spawn. The success of aquaculture could therefore be improved by developing techniques to enhance natural spawning, artificial maturation, and/or to induce ovulation in farmed fish. This study aimed to investigate the effects of prostaglandin $E_2$ ($PGE_2$) and prostaglandin $F_{2{\alpha}}$ ($PGF_{2{\alpha}}$) on in vitro oocyte maturation (germinal vesicle breakdown, GVBD) and ovulation in the marine fish Chasmichthys dolichognathus. Post-vitellogenic follicles (0.80-0.94 mm diameter oocytes) were incubated with $PGE_2$ or $PGF_{2{\alpha}}$ at concentrations of 5, 50, or 500 ng/mL for 24 hours. A significant increase in GVBD was seen in 0.84 mm and 0.94 mm oocytes incubated with 50 ng/mL $PGE_2$ compared with the control. There was no significant increase in GVBD in any of the other experimental conditions (5 or 500 ng/mL $PGE_2$ or 5, 50, or 500 ng/mL $PGF_{2{\alpha}}$). Neither of the prostaglandins induced ovulation at the concentrations tested.These results suggest that GVBD was induced by incubation with 50 ng/mL $PGE_2$.