• 대한한의학회지
• /
• 제26권4호
• /
• pp.152-161
• /
• 2005

The excessive release of proinflammatory products by activated microglia causes neurotoxicity, and this has been implicated in the pathogenesis of neurodegenerative diseases. Harpagophytum procumbens (Pedaliaceae) has been widely used for the treatment of pain and arthritis in the clinical field. In this study, we investigated the effect of Harpagophytum procumbens against lipopolysaccharide-induced inflammation. From the present results, the aqueous extract of Harpagophytum procumbens was shown to suppress prostaglandin-E2 synthesis and nitric oxide production by inhibiting the lipopolysaccharide-stimulated enhancement of cyclooxygenase-2 and inducible nitric oxide synthase expressions in mouse BV2 microglial cells. These results suggest that Harpagophytum procumbens may offer a valuable means of therapy for the treatment of brain inflammatory diseases by attenuating lipopolysaccharide-induced prostaglandin-E2 synthesis and nitric oxide production.

• Natural Product Sciences
• /
• 제18권4호
• /
• pp.211-214
• /
• 2012

Since 15-hydroxyprostaglandin dehydrogenase (15-PGDH) is the key metabolic enzyme of prostaglandin $E_2$ ($PGE_2$), inhibition of 15-PGDH is supposed to facilitate various physiological functions by increasing $PGE_2$. Methanol extract of Artemisia argyi (AAME) inhibited 15-PGDH ($IC_{50}$: $13.13{\mu}g/mL$) with relatively low cytotoxicity ($IC_{50}$: $415.00{\mu}g/mL$) and elevated extracellular $PGE_2$ levels in HaCaT cells. Real-time PCR analysis showed that AAME decreased significantly mRNA expression of PG transporter (PGT) in HaCaT cells. These results indicate that AAME could be applicable to functional materials as a 15-PGDH inhibitor and PGT expression inhibitor for the upregulation of extracellular $PGE_2$ level.

• 한국한의학연구원논문집
• /
• 제7권1호
• /
• pp.115-124
• /
• 2001

Yukmijihwangwon (YM) has been known to reinforce the vital essence and have antioxidant activities. This study was designed to examine the inhibitory effects of YM against in vitro hypoxia/reperfusion-induced inflammatory response. We have characterized the production of prostaglandin $E_2$ and arachidonic acid during hypoxia/reperfusion in the human neuroblastoma SK-N-MC and human monocytic macrophage U937 cells and the ingibitory effect of YM on these inflammation-related substance formation has been found out in this study. To investigate inhibition of COX expression by YM during hypoxia in vitro. This result suggested that YM used in this experiment reinforced antiinflammatory potentials and protected cells against hypoxia/reperfusion induced inflammatory response.

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

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

• 예술인문사회 융합 멀티미디어 논문지
• /
• 제9권6호
• /
• pp.443-450
• /
• 2019

본 연구에서는 갈퀴나물(Vicia amoena) 전초를 이용한 에탄올 추출물의 세포독성과 항염증 활성 효과를 평가하였다. RAW264.7 cell(대식세포)에서 염증 매개 물질인 lipopolysaccharide(LPS)로 염증을 유발시켜 nitric oxide (NO) 및 prostaglandin E₂ (PGE₂)같은 염증 유발 인자들의 생성 저해효과를 확인하였다. 갈퀴나물 에탄올 추출물의 염증 유발 인자 억제 시 저해효과를 측정하였을 때 nitric oxide 및 prostaglandin E₂ 생성을 농도 의존적으로 현저하게 저해하는 농도인 40 ㎍/㎖의 농도에서 LPS에 의해 유도된 NO를 36.0 ± 0.5 % 저해하였으며, 특히 PGE₂에서는 88.0 ± 0.8 % 만큼 유의성 있는 저해효과를 나타내었다. 따라서 본 연구결과는 갈퀴나물의 에탄올 추출물이 유의성 있는 항염증 효과를 나타내며, 이러한 효능은 예방의학적 가능성을 충분히 가지고 있기에 염증성 질환의 예방을 위한 항염증 소재로의 개발 가능성을 제시할 수 있을 것으로 기대된다. 차후 에탄올 추출물의 보다 다양한 농도 및 유기용매 분획물에서 염증반응을 매개하는 iNOS·COX-2 등 의 다양한 효소의 발현과 Iκ-Bα의 분해 등 염증반응의 신호전달물질의 변화에 대한 추가적인 연구가 필요할 것으로 판단된다.

• Biomolecules & Therapeutics
• /
• 제3권1호
• /
• pp.72-79
• /
• 1995

The antiulcer effects of newly synthesized prostaglandin derivatives were investigated in various experimental ulcer models and on gastric secretion in rats. HK-3 and HK-4, PG $E_2$derivatives, prevented the formation of acute gastric ulcer induced by ethanol or aspirin in pylorus-ligated rats. The ulcer formation was moderately inhibited by HK-1 and HK-2, PG $F_{2{\alpha}}$ derivatives, and aggravated by SK-1, SK-2 and SK-3, PG $F_{2{\alpha}}$ derivatives. HK-3 and HK-4 reduced the volume, acid output and pepsin output of gastric juice in pylorus-ligated rats. The gastric perfusion with physiologic saline(pH 6.0) showed relatively constant acid secretion and indomethacin increased the acid secretion. The acid secretion was markedly decreased by PG $E_2$but PG $F_{2{\alpha}}$ caused little change. Prostaglandin derivatives, especially HK-3 arid HK-4, significantly inhibited the acid secretion induced by indomethacin. The results show that, PG $E_2$ derivatives, HK-3 and HK-4, inhibit acid secretion and also have protective effects on gastric ulceration induced by ethanol or aspirin.

• Journal of Pharmaceutical Investigation
• /
• 제34권2호
• /
• pp.107-114
• /
• 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 $PGE_1$.

• Journal of Pharmaceutical Investigation
• /
• 제29권4호
• /
• pp.337-341
• /
• 1999

We have studied the stability and transdennal flux of prostaglandin $E_1\;(PGE_1)$ from various donor solutions through hairless mouse skin. Stability in HEPES buffer or in propylene glycol (PG) solution where enhancer (oleic acid (OA), propylene glycol monolaurate (PGML), transcutol (TC), ethanol (EtOH))s dissolved was investigated. $$PGE_1 was not stable in HEPES buffer. The concentration of $$PGE_1 decreased continuously for 7 days, and the degradation rate constant was $0.0028\;h^{-1}$, assuming first order reaction. The effect of current or penetration enhancer on the degradation was minimal. Percutaneous transport from HEPES buffer by passive or iontophoretic delivery without enhancer was close to nil. When OA or PGML was used together with PG, both passive and iontophoretic flux increased. PGML showed better enhancing effect than OA. Flux by cathodal delivery was about 2 times larger than that by passive delivery. Flux by anodal delivery was lower than that by passive delivery. TC and EtOH also increased the transdermal flux, but the effect was not as good as that observed when OA or PGML was used. These stability and flux data provide important information on how to formulate the patch, which will be the next step of this work, and on the polarity of current to use during iontophoresis.

• BMB Reports
• /
• 제41권11호
• /
• pp.808-813
• /
• 2008

Human microsomal prostaglandin E synthase-1 (mPGES-1) is a membrane associated protein that catalyzes the conversion of prostaglandin $H_2$ ($PGH_2$) into prostaglandin $E_2$ ($PGE_2$). In this study, the expression of human mPGES-1 in E. coli was significantly enhanced by modifying the utility of specific codons and the recombinant mPGES-1 was efficiently purified to homogeneity. The $K_m$ and $V_{max}$ of the purified enzyme were determined and the trimeric state characterized by chemical cross-linking with glutaraldehyde. The purified mPGES-1 was used for the screening of a chemical library of bioactive or drug compounds to identify novel inhibitors, and oxacillin and dyphylline were identified as moderately inhibiting mPGES-1 with $I_{C50}$ values of 100 and 200 ${\mu}M$, respectively. As these compounds competitively inhibited the catalysis of $PGH_2$, their binding sites appeared to be located near the $PGH_2$ binding pocket.