• 한국자원식물학회:학술대회논문집
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• 한국자원식물학회 2023년도 임시총회 및 춘계학술대회
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• pp.50-50
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• 2023

Prostaglandin E2(PGE2), a major product of cyclooxygenase-2 (COX-2), plays an important role in the carcinogenesis of many solid tumors, including colorectal cancer. Because PGE2 functions by signaling through PGE2 receptors (Eps), which regulate tumor cell growth, invasion, and migration, there has been a growing amount of interest in the therapeutic potential of targeting Eps. In the present study, we investigated the role of EP4 on the effectiveness of cordycepin in inhibititing the migration and invasion of HCT116 human colorectal carcinoma cells. Our data indicate that cordycepin suppressed lipopolysaccharide (LPS)-enhanced cell migration and invasion through the inactivation of matrix metalloproteinases (MMP)-9 as well as the down-regulation of COX-2 expression and PGE2 production. These events were shown to be associated with the inactivation of EP4 and activation of AMP-activated protein kinase (AMPK). Moreover, the AMPK inhibitor, compound C, as well as AMPK knockdown via siRNA, attenuated the cordycepin-induced inhibition of EP4 expression. Cordycepin treatment also reduced the activation of CREB. These findings indicate that cordycepin suppresses the migration and invasion of HCT116 cells. Through modulating EP4 expression and the AMPK-CREB signaling pathway. Therefore, cordycepin has the potential to serve as a potent anti-cancer agent in therapeutic strategies against colorectal cancer metastasis.

• 고려인삼학회:학술대회논문집
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• 고려인삼학회 1988년도 학술대회지
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• pp.77-80
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• 1988

인삼의 효과는 인삼칠효설로 요약되듯이 각종 장기에 대하여 다양한 약리작용을 나타낸다. 이는 인삼의 약리작용을 중개하는 생체내 생리활성물질의 존재를 생각하게 되며 이같이 생리활성물질을 하나로 prostaglandin을 들 수 있다. 본 연구에서는 인삼성분이 prostaglandin 등 arachidonic acid 대사산물 생성에 미치는 영향을 실험함으로써 인삼의 약리학적 작용과 그 기전을 간접적으로 구명하고자 하였다. 즉 $[^{3}H]$-arachidonic acid를 기질로 넣어주고 토끼 신장 microsome, 소 대동맥 microsome, 사람 혈소판 homogenate 등을 효소원으로 한 in vitro 생합성과정에 변화를 주는 수종 인삼 saponin 및 phenolic acid 성분의 효과를 검정하였다. 실험에 사용한 인삼 saponin 성분은 panaxadiol, panaxatriol 및 protopanaxadio 계 saponin 류인 ginsenoside $Rb_{2}(G-Rb_{2})$, ginsenoside Rc(G-Rc) 및 protopanaxatriol 계 saponin류인 ginsenoside Re(G-Re) 이었고 이들 성분이 arachidonic acid로부터 cyclooxygenase를 통해 최종 대사산물인 prostaglandin 류를 생성하는 과정에 미치는 영향을 관찰하여 다음과 같은 결과를 얻었다. 1. Arachidonic acid 로부터 생성된 총 cyclooxygenase 반응생성물 및 malondialdehyde의 양은 실험에 사용한 인삼 saponin 성분의 전 농도 범위에서 유의적인 변화를 보이지 않았는데 이는 인삼 saponin 성분들은 cyclooxygenase에 직접 작용하지 않는다는 것을 설명해 준다. 2. Panaxadiol (500 ${\mu}g/ml$은 $PGE_{2}$ 생성에는 영향이 없으나 $PGF_{2}{\alpha}$생성에 유의적인 차이를 보이지 않으나 농도의존적으로 $TxB_{2}$의 생성을 감소시켰고 6-keto-$PGF_{1}{\alpha}$의 생성을 증가시켰는데 이는 $TxA_{2}$ synthetase 억제제인 imidazole의 효과와 유사하였다. 4. G-Re는 $1{\times}10^{-5}g/ml$ 이하의 농도에서는 효과가 없으나 $1{\times}10^{-4}g/ml$ 이상의 농도에서 농도의존적으로 유의성 있는 $PGE_{2},\;PGF_{2}{\alpha},\;TXB_{2}$의 생성억제와 함께 6-keto-$PGF_{1}{\alpha}$ 증가를 보였다. 이는 prostacyclin synthetase를 자극하는 serotonin의 효과와 같은 작용으로서 prostacyclin synthetase 억제제인 tranylcypromine에 대하여 길항효과를 보였다. 5. $TxB_{2}$생성억제 작용을 나타내는 ginsenoside들의 효과를 뒷받침하기 위하여 인삼 saponin 성분을 전처치한 patelet rich plasma에서 혈소판 응집시험 결과, ADP로 유도된 혈소판 응집반응에는 모든 인삼 saponin 성분들이 효과가 없었으나 arachidonic acid로 유도된 혈소판 응집반응에는 $G-Rb_{2}$, G-Rc, G-Re의 순으로 농도 의존적인 억제현상을 보였다. 이상의 결과와 같이 인삼 saponin 성분들은 arachidonic acid로부터 cyclooxygenase를 통해 일단 생성된 endoperoxide에서 각각의 prostaglandin을 생성하는 효소, 특히 $G-Rb_{2}$는 $TxA_{2}$ sysnthetase에 강력한 억제제로, G-Re는 prostacyclin 생합성의 촉진제로 심혈관계 균형에 기여하리라 생각된다.

• 대한약리학회지
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• 제19권2호
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• pp.1-8
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• 1983

Prostaglandin(PG) is ubiquitously distributed in most mammalian tissue and their actions are complicated. Especially in autonomic nervous system, there are evidences indicating that PGs act as neuromodulators i.e., PGs, which are released in the vicinity of autonomic neuroeffector junctions, influence the release and the response of the neurotransmitter. Present study was undertaken to elucidate the interrelationship between $PGF_{2\alpha}$ and adrenergic ${\alpha}_2-receptor$ function in electrical field stimulation induced contractile response of vas deferens in rat. Male rat, weighing 150{\sim}200\;g, was sacrificed and vas deferens was obtained. The isolated vas deferens strip was placed between two platinum electrodes in temperature controlled $(37^{\circ}C)$ muscle chamber containing Tyrode's solution and the electrical field stimulation(EFS) induced contraction was recorded with Grass Polygraph(Model 7) via force displacement transducer (FT .03, Grass). The results are summarized as follows: 1) Electrical field stimulation for 1sec( 1 msec, 40 cps) induced contraction of vas deferens was completely blocked by tetrodotoxin. 2) Bretylium caused marked inhibition of the EFS-induced contraction, hut tyramine and cocaine augmented the contraction. 3) EFS-induced contraction was inhibited or little affected in distal portion of vas deferens by norepinephrine or methoxamine, but the contraction was rather augmented by the ${\alpha}-agonists$ in proximal portion. 4) Clonidine inhibited the EFS-induced contraction proportionally to the concentration in distal portion, which was blocked by yohimbine pretreatment, but in the presence of $PGF_{2\alpha}$ the blockade by yohimbine was reversed. 5) Indomethacin pretreatment reduced the effect of clonidine, but addition of $PGF_{2\alpha}$ after washing-out the indomethacin caused the contraction to the control level. From these results it is suggested that PG synthesis is a necessary step and the PG itself has a permissive role in ${\alpha}_2-adrenoceptor$ action in rat vas deferens.

• Asian Pacific Journal of Cancer Prevention
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• 제13권4호
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• pp.1639-1644
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• 2012

The aim of this study was to investigate the expression and significance of microsomal prostaglandin synthase-1 (mPGES-1) and Beclin-1 in the development of prostate cancer (PCa). Immunohistochemistry was performed on paraffin-embedded sections with rabbit polyclonal against mPGES-1 and Beclin-1 in 40 PCa, 40 benign prostatic hyperplasia (BPH) and 10 normal prostate specimens for this purpose. Quantitative real-time polymerase chain reaction (qRT-PCR) was applied for mRNA expression of mPGES-1 and Beclin-1, while MTT assays were used to ascertain the best working concentration of the mPGES-1 inhibitor (CAY10526). The effect of CAY10526 treatment on expression of Beclin-1 in DU-145 cells was studied using Western blot analysis. Localization of Beclin-1 and mPGES-1 was in endochylema. Significant differences in expression was noted among PCa, BPH and normal issues (P<0.05). Beclin-1 expression inversely correlated with mPGES-1 expression in PCa tissue (P<0.05). CAY10526 could significantly block mPGES-1 expression and the proliferation of DU-145 cells (P<0.05), while increasing Beclin-1 levels (P<0.05). Overexpression of mPGES-1 could decrease the autophagic PCa cell death. Inhibiting the expression of mPGES-1 may lead to DU-145 cell death and up-regulation of Beclin-1. The results suggest that inhibition of mPGES-1 may have therapeutic potential for PCa in the future.

• Asian-Australasian Journal of Animal Sciences
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• 제19권6호
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• pp.793-798
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• 2006

The quality characteristics of semen are important indicators of the fertility of a boar. Development of genetic markers for the semen quality in boars will be beneficial to the improvement of porcine fertility. We investigated the relationship between the polymorphisms of epidermal growth factor (EGF), prostaglandin-endoperoxide synthase 2 (PTGS2) and prolactin receptor (PRLR) genes, and semen quality traits in boars. The genomic DNA of 233 boars (157 Duroc and 86 Landrace) from a central testing station was subjected to genotyping for surveying gene frequency. The EGF, PTGS2 and PRLR genotypes were determined using the restriction fragment length polymorphism method. Thirty-seven normal, mature Duroc boars from an AI center were also genotyped and their semen quality traits were collected. The effect of genotype on semen quality traits was analyzed by the least-squares means method using data corrected for season. The frequencies of the AA genotype of EGF, PTGS2 and PRLR in Duroc boars were 0.14, 0.01 and 0.66, respectively. In Landrace, the frequencies of the AA genotype were 0.03, 0.09 and 0.62, respectively. Boars with the BB genotype in EGF, with the AB genotype in PTGS2 and with the AA genotype in PRLR had significantly better semen quality with a higher percentage of normal sperm and a lower percentage of immature sperm than those with other genotypes. These findings imply that polymorphisms of EGF, PTGS2 and PRLR genes might be used as markers for improving the semen quality of boars.

• 한국발생생물학회지:발생과생식
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• 제15권1호
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• pp.17-24
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• 2011

Lipid metabolites involved in cellular regulation as signaling mediators. Prostaglandins (PGs), metabolites of lipid are involved to pregnancy at the time of implantation but the functional roles of PGs on embryo development are still controversy and largely unknown. In previous report, the levels of $PGE_2$ and $PGF_{2a}$ at embryos of morula stage and blastocyst stage were explored (Cheon et al., 1998). In this study, the previous suggestion was confirmed and the possible downstream mediator of prostaglandin $E_2$ and prostaglandin $F_{2a}$ on the expansion and hatching of mouse embryo was examined. As expected, developmental rate of the blastocyst to expanded stage was a concentration-response curve that showed the highest expansion rate at 10 ${\mu}M$ $PGE_2$, but at 100 ${\mu}M$ $PGE_2$, the rate was decreased. In contrast to the $PGE_2$, $PGF_{2a}$ stimulated expansion without toxicity at highest concentration. Cotreatment of PGs with indomethacin overcame the inhibitory effects of indomethacin in expansion. Exogenous PGs also improved the development of expanded embryos to the hatching stage. Besides, PGs receptors' transcripts detected at blastocyst. $PGE_2$ was caused of calcium fluctuation in the blastocyst but $PGF_{2a}$ did not. The changes of intracellular calcium concentration were different between indomethacin pretreated embryos and non-treated embryos. Based on these results it is suggested that PGs work as paracrine and/or autocrine factors through calcium and the others which were not identified in this study.

• 한국양식학회지
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• 제11권4호
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• pp.513-519
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• 1998

인간의 태반성 성선자극 호르몬(HCG) 또는 성선자극 호르몬-방출 호르몬 유도체(GnRH-a) 단독 주사와 HCG+GnRH-a, GnRH-a+prostaglandin E sub(2) (PGF sub(2)), GnRH-a+pimozide를 복합적으로 주사하여 성숙한 암컷 쏘가리에서 배란 유도 실험을 하였다. 호르몬과 유도체의 반응 효과는 배란후 인공 수정하여 수정율과 배체형성율을 측정하여 결정하였다. 일반적으로 GnRH-a 실험군이 HCG 실험군에 비해서 수정율과 배체형성율 및 부화율이 높았다. HCG(5,000 IU/kg)+(GnRH-a(10 ${\mu}$g), GnRH-a(10 ${\mu}$g/kg)+PG$F^2$(500 ng/kg) 및 GnRH-a(10 ${\mu}$g/kg)+pimozide(1-5 mg/kg)에서 89% 이상의 높은 부화율을 보였다. 본 연구에서 사용된 성성숙 호르몬과 자극물질로 처리된 모든 암컷에서 배란이 유도되었지만, HCG+GnRH-a+dopamine과 GnRH-a+PG$F_2$+indometacin 처리군에서는 배란이 억제되었다. 이들의 결과는 산란시기에 여러 가지 성성숙 호르몬과 관련된 호르몬과 성성숙 억제물질(GRIF)이 분비된다는 점을 시사한다.

• Archives of Pharmacal Research
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• 제28권7호
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• pp.848-853
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• 2005

Synurus deltoides was previously found to possess significant anti-inflammatory activity especially against chronic inflammation, and strong analgesic activity in vivo. In this study, new anti-inflammatory formulation containing S. deltoides extract as a major ingredient was prepared and in vivo activity was evaluated. The plausible action mechanism was also investigated. The new formulation (SAG) contains 1 part of S. deltoides extract, 0.9 part of Angelica gigas extract and 0.9 part of glucosamine sulfate (w/w). SAG inhibited dose-dependently edematic response of arachidonic acid (AA)- and 12-O-tetradecanoyl 13-acetate (TPA)-induced ear edema in mice, which is an animal model of acute inflammation. SAG showed 44.1 % inhibition of AA-induced ear edema at an oral dose of 50 mg/kg. In an animal model of chronic inflammation, SAG clearly reduced the edematic response of 7 -day model of multiple treatment of TPA (38.1 % inhibition at 200 mg/kg/day). Furthermore, SAG (50-800 mg/kg/day) as well as S. deltoides extract (285 mg/kg/day) significantly inhibited prostaglandin $E_2$ production from the skin lesion of the animals of 7-day model. These results were well correlated with in vitro finding that SAG as well as S. deltoides extract reduced cyclooxygenase (COX)-1- and COX-2-induced prostanoid production, measured in mouse bone marrow-derived mast cells. Therefore, these results suggest that SAG possesses anti-inflammatory activity in vivo against acute as well as chronic inflammatory animal models at least in part by inhibition of prostaglandin production through COX-1/COX-2 inhibition. And COX inhibition of SAG is possibly contributed by S. deltoides extract among the ingredients. Although the anti-inflammatory potencies of SAG were less than those of currently used anti-inflammatory drugs, this formulation may have beneficial effect on inflammatory disorders as a neutraceutical.

• 한국환경성돌연변이발암원학회:학술대회논문집
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• 한국환경성돌연변이발암원학회 2002년도 Molecular and Cellular Response to Toxic Substances
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• pp.187-187
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• 2002

• Journal of Chest Surgery
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• 제20권2호
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• pp.432-437
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• 1987

Pulmonary atresia with intact ventricular septum is a extremely rare congenital cardiac anomaly. With the history of cyanosis and failure to thrive, this anomaly should not be excluded and emergency management is necessary. Our patient was 69 day-old male with pulmonary atresia which was confirmed by cardiac angiography. Prostaglandin E1 was used for maintenance of pulmonary blood flow preoperatively. Right ventricular outflow reconstruction with pericardial patch and concomitant pulmonary valvotomy were done on beating heart for palliation. With this method, growing of right ventricle and tricuspid annulus are highly expected.