• Journal of Pharmaceutical Investigation
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• v.35 no.5
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• pp.375-381
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• 2005

A rapid and specific high-performance liquid chromatographic method was developed and validated for the simultaneous determination of prostaglandin $E_{1}\;(PGE_{1})$ and prostaglandin $E_{1}$ ethyl ester $(PGE_{1}-EE)$ in hairless mouse skin homogenate. The sample treatment procedure involved deproteination and precipitation by acetonitrile. $PGE_{1}$ and $PGE_{1}-EE$ in supernatant were separated in a reversed-phase C18 column without being interfered by other components present in hairless mouse skin homogenate. 9-Anthracenecarboxylic acid was used as an internal standard. The retention times of $PGE_{1}$, 9-anthracenecarboxylic acid and $PGE_{1}-EE$ were, 4.5, 9.5 and 18.0 min, respectively. The assay showed linearity from 1 to $40\;{\mu}g/ml$ for both $PGE_{1}$ and $PGE_{1}-EE$. Precision expressed as RSD ranged from 2.3 to 14.1 % for $PGE_{1}$ and 1.6 to 11.0% for $PGE_{1}-EE$. Accuracy ranged from 100.5 to 119.6 % for $PGE_{1}$ and from 98.0 to 103.7% for $PGE_{1}-EE$. This method was employed successfully to follow the time course of concentrations of $PGE_{1}$ and $PGE_{1}-EE$ in hairless mouse skin homogenate for stability study.

• Korean Journal of Pharmacognosy
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• v.47 no.4
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• pp.295-300
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• 2016

Flavonoids are widely reported to be beneficial to human health. Among flavonoids, in general, flavonoid aglycons have better biological activities than flavonoid glycosides, in that aglycons can easily penetrate through cell membrane because of their low polarity. Therefore, kaempferol, quercetin and various their glycosides were evaluated for their abilities to inhibit NO and $PGE_2$ productions in LPS-induced RAW 264.7 cells. Of these flavonoids and flavonoid glycosides, kaempferol-7-O-${\beta}$-D-glucoside(kp-7-glu) which possesses a glycoside at C-7 position of the A ring in kaempferol, potently inhibited NO, $PGE_2$ and $TNF-{\alpha}$, $IL-1{\beta}$, IL-6 productions in LPS-induced RAW 264.7 macrophages.

• Herbal Formula Science
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• v.27 no.4
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• pp.245-255
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• 2019

Objective : Herbal processing is one of the traditional techniques used in Korean medicine to increase the effectiveness of herbs or reduce their toxicity. In this study, Gardeniae Fructus processed with ginger juice and alcohol was prepared to evaluate the anti-inflammatory effect on lipopolysaccharide (LPS)-induced macrophages. Methods : The processing of Gardeniae Fructus was performed by adding 40 % ginger juice or 10% alcohol to the total weight of Gardeniae Fructus and then roasting at 150℃ for 5 minutes. Cell viability was determined by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. To detect nitric oxide (NO) production, culture media were mixed with Griess reagent and measured the absorbance at 540 nm. Prostaglandin E₂ (PGE₂) and pro-inflammatory cytokines were detected by enzyme-linked immunosorbent assay (ELISA). Western blot was applied to monitor protein expression levels. Results : LPS-induced NO, PGE₂ and inflammatory cytokines were decreased by the treatment of normal or processed Gardeniae Fructus ethanol extracts (GFE). Compared to normal GFE, the processed GFE showed a stronger inhibitory effect on the production of NO and PGE₂. These inhibitory effect of GFE was due to the suppression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) mediated from the inhibition of nuclear factor kappa B (NF-κB). Furthermore, processed GFE showed more suppressive effects on the expression of iNOS, COX-2 and IκBα proteins than normal GFE. Conclusion : From these results, it was concluded that GFE had an improved anti-inflammatory effect compared to normal GFE. These results provide an objective evidences for the use of herbal processing in Korean medicine.

• Journal of Physiology & Pathology in Korean Medicine
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• v.34 no.1
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• pp.7-13
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• 2020

Sanyeoleumja (SY) is the traditional Korean medicinal prescription for the treatment of inflammatory diseases of eyes. In this study, the anti-inflammatory effects of SY water extract were investigated. To measure the anti-inflammatory effects of SY, we examined the productions of inflammatory factor including nitric oxide (NO), prostaglandin E2 (PGE₂), inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), interleukin-6 (IL-6), interleukin-1β (IL-1β) in lipopolysaccharide (LPS)-induced RAW 264.7 cells. SY inhibited NO and PGE₂ production in a dose dependent manner and decreased the protein and mRNA expression of iNOS and COX-2. Also, SY decreased the mRNA expression of interleukin-6 (IL-6) and interleukin-1β (IL-1β). In conclusion, SY downregulated LPS-induced inflammatory factor productions, which could be a clinical basis for inflammatory diseases.

• 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 $PGE_1$.

• The korean journal of orthodontics
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• v.20 no.1
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• pp.61-86
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• 1990

To study the effect of prostglandin $E_2$ and evening primrose oil on orthodontic tooth movement in rats, one hundred and sixty rats were divided into four groups of 40 rats each. One group, injected with saline on the palate subperiosteally, served as a control group. A second and third group were injected subperiosteally on the palate with $PGE_2$ $10{\mu}g$ and evening primrose oil 10mg respectively. The fourth group was given indomethacin $20{\mu}g/m{\ell}$ orally by water bottle. The maxillary first molar was moved mesially from the incisors using a 50gm force rubber band. In each group at the 1, 2, 3, 5, and 7th day, 4 rats were examined by light microscope, and 4 by electron microscope. The obtained results were as follows: 1. Osteoclastic activity was maximum at the 3rd day in the $PGE_2$ group on the interradicular alveolar bone of the first molar, followed by the evening primrose oil group, control group, and indomethacin group. 2. Root resorption and vacuolar changes were maximum in the $PGE_2$ group. 3. At the 3rd day of the $PGE_2$ group, the osteoclasts showed well developed ruffled borders and clear zones. At the same day, the evening primrose oil group also showed well developed ruffled borders and clear zones, but less than the $PGE_2$ group. 4. At the 3rd and 5th day of the $PGE_2$ group, fibroblasts showed phagocytized fragmented collagen fibers in the cytoplasm. At the 7th day of the $PGE_2$ group, fibroblasts showed collagen fibers forming at the cell membrane surface.

• Korean Journal of Medicinal Crop Science
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• v.22 no.6
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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.

• BMB Reports
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• v.48 no.2
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• pp.109-114
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• 2015

The COX-2/$PGE_2$ pathway has been implicated in the occurrence and progression of cancer. The underlying mechanisms facilitating the production of COX-2 and its mediator, $PGE_2$, in cancer survival remain unknown. Herein, we investigated $PGE_2$-induced COX-2 expression and signaling in HL-60 cells following menadione treatment. Treatment with $PGE_2$ activated anti-apoptotic proteins such as Bcl-2 and Bcl-xL while reducing pro-apoptotic proteins, thereby enhancing cell survival. $PGE_2$ not only induced COX-2 expression, but also prevented casapse-3, PARP, and lamin B cleavage. Silencing and inhibition of COX-2 with siRNA transfection or treatment with indomethacin led to a pronounced reduction of the extracellular levels of $PGE_2$, and restored the menadione- induced cell death. In addition, pretreatment of cells with the MEK inhibitor PD98059 and the PKA inhibitor H89 abrogated the $PGE_2$-induced expression of COX-2, suggesting involvement of the MAPK and PKA pathways. These results demonstrate that $PGE_2$ signaling acts in an autocrine manner, and specific inhibition of $PGE_2$ will provide a novel approach for the treatment of leukemia.

• Archives of Reconstructive Microsurgery
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• v.9 no.2
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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.

• Biomedical Science Letters
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• v.27 no.4
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• pp.223-230
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• 2021

Tumor necrosis factor alpha (TNF-α) is a principal regulator of inflammation and immunity. The proinflammatory properties of TNF-α can be attributed to its ability to activate the enzyme cytosolic phospholipase A₂ (cPLA₂), which generates potent inflammatory lipid mediators, eicosanoids. L-glutamine (Gln) plays physiologically important roles in various metabolic processes. We have reported that Gln has a potent anti-inflammatory activity via rapid upregulation of mitogen-activated protein kinases (MAPKs) phosphatase (MKP)-1, which preferentially dephosphorylates the key proinflammatory enzymes, p38 MAPK and cytosolic phospholipase A₂ (cPLA₂). In this study, we have investigated whether Gln could inhibit TNF-α-induced cPLA₂ activation. Gln inhibited TNF-α-induced increases in cPLA₂ phosphorylation in the lungs and blood levels of the cPLA₂ metabolites, leukotrine B4 (LTB4) (lipoxygenase metabolite) and prostaglandin E2 (PGE2) (cyclooxygenase metabolite). TNF-α increased p38 and cPLA₂ phosphorylation and blood levels of LTB4 and PGE2, which were blocked by the p38 inhibitor SB202190. Gln inhibited TNF-α-induced p38 and cPLA₂ phosphorylation and production of the cPLA₂ metabolites. Such inhibitory activity of Gln was no longer observed in MKP-1 small interfering RNA-pretreated animals. Our data indicate that Gln inhibited TNF-α-induced cPLA₂ phosphorylation through MKP-1 induction/p38 inhibition, and suggest that the utility of Gln in inflammatory diseases in which TNF-α plays a major role in their pathogenesis.